2019 Positively Aware Hiv Drug Guide Opening Credits

Home , Vidarabine

YOUR TICKET TO THE MOST COMMONLY PRESCRIBED MEDICATIONS FOR TREATING HIV WITH INSIGHT FROM AN HIV SPECIALIST AND AN ACTIVIST

POSITIVELY AWARE HIV TREATMENT, PREVENTION, AND SUPPORT FROM TPAN MARCH+APRIL 2019

THE 23 RD ANNUAL HIV DRUG GUIDE WITH PULL-OUT HIV DRUG CHART

AN CLIFFHANGER AND THE ON WITH ENSEMBLE CAST FOR A CURE NOMINEES ARE... THE SHOW! How drug classes We’re ready for a cure— Recommendations Moving beyond play their parts aren’t we? for first-time therapy your diagnosis POSITIVE ROLES: LEFT TO RIGHT, TOP ROW: JOSEPH HUTTO, DANIELLE KRUSE, ARMANDO RAMIEREZ GUZMAN. MIDDLE ROW: D EVA LONGORIA, JOSHUA F. STOVALL, DOUG FERGUSON. BOTTOM ROW: JUDY BROWN, RENÉ GARZA, DUANE CRAMER.

POSITIVELY AWARE JOURNALISM. INTEGRITY. HOPE.

Jeff Berry EDITOR-IN-CHIEF @PAeditor

Enid Vázquez ASSOCIATE EDITOR @enidvazquezpa

Rick Guasco CREATIVE DIRECTOR @rickguasco

PROOFREADER Jason Lancaster

CONTRIBUTING WRITERS David Durán Andrew Reynolds Michelle Simek Warren Tong

PHOTOGRAPHERS John Gress Chris Knight

ADVERTISING MANAGER Lorraine Hayes [email protected]

DISTRIBUTION MANAGER & SUBSCRIPTION SERVICES Denise Crouch [email protected]

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TPAN was founded in 1987 in Chicago as Test Positive Aware Network, when 17 individuals gathered in a living room to share information and support in response to the HIV/AIDS epidemic. POSITIVELY AWARE is the expression of TPAN’s mission to share accurate, reliable, and timely treatment information with anyone affected by HIV.

2 MARCH + APRIL 2019 | POSIT IVELY AWARE PHOTO: While the experience Understanding drug interactions. MARCH is your own, you’re AND THE NOMINEES THE ARE... AND We’re HIV cure— an for ready HIV treatment can be costly, be HIV treatment can WHEN DRUGS COLLIDE! WHEN DRUGS COLLIDE! FRONT COVER COVER FRONT DHHS recommendations BACKSTORY BACKSTORY ON WITH THE SHOW! SHOW! THE WITH ON BY W.BY DAVID HARDY, MD beyond your diagnosis. beyond not alone. SUPPORTING ROLE ROLE SUPPORTING W. DAVID HARDY, MD HARDY, W. BY DAVID COMMENTS for frst-time therapy.for CLIFFHANGER Moving forward Moving forward but there’s help. 4 —with comments from a specialist and an HIV activist. HIV activist. an and aspecialist —with from comments VOLUME VOLUME FOR A CURE ACURE FOR A handbook of the medications used for treating for HIV used of the medications A handbook aren’t we? w~~ 20 23 10 19 13 FOR A LIST OF WALGREENS HIV SPECIALTY PHARMACIES, PHARMACIES, SPECIALTY HIV WALGREENS OF ALIST FOR BY BY AND OTHER RESOURCES, GO TO HIV.WALGREENS.COM TO GO RESOURCES, OTHER AND 2019 PULL-OUT HIV DRUG CHART SPONSORED BY BY SPONSORED CHART DRUG HIV PULL-OUT 2019 29 ENID VÁZQUEZ ENID NUMBER NUMBER HIV DRUG GUIDE DRUG HIV 23RD ANNUAL POSITIVELY AWARE THE CONVERSATION POSITIVELY AWARE + Mixed emotions. emotions. Mixed E V E R Y I S S U E 28–69 28–69 Get yours now. yours Get 2 positivelyaware.com positivelyaware.com AND ERIC K. FARMER, AND APRIL APRIL 6 Trusted since1901'" MOISÉS AGOSTO-ROSARIO MOISÉS AGOSTO-ROSARIO AND medications inmedications the drug guide. OUR OF YOUR DRUG GUIDE long-term suvivors and older older and long-term suvivors A new collaboration focuses focuses collaboration A new How diferent drug classes How diferent drug classes COMING ATTRACTIONS play their part to fghtplay HIV. their part on practical solutionson practical for Tips for using for thisTips guide. new drugs coming soon. drugsnew coming soon. AN ENSEMBLE CAST CAST ENSEMBLE AN GETTING THE MOST MOST THE GETTING An Ato ZlistingAn of the POSITIVELY AGING adults living with HIV. A sneak peak at the peak A sneak | MARCH + APRIL 2019 2019 +APRIL MARCH | JEFF BERRY BERRY JEFF BY P PLACES! PLACES! HARM Instead of hurrying Instead of hurrying @posaware 70 26 72 through life, take 71 27 a moment, and a moment, and EDITOR’S NOTE 2019 2019 D

breathe. breathe. 7 3 2019 POSITIVELY AWARE FRONT COVER HIV DRUG GUIDE BACKSTORY The experience is your own, but you’re not alone in the room

HERE’S SOMETHING to be said about sitting in a darkened room with a bunch of a strangers, watching a flm in a movie theater. Everyone is sharing the same expe- Trience, but how they react is uniquely their own response. That’s the concept behind the cover of this year’s HIV drug guide. The nine people who took part in the drug guide cover shoot are all living with HIV. They shared their experiences and insights.

Armando Ramirez-Guzman, 38, has been living with HIV since 2003. The cover’s concept resonated with him: “I not only advocate, I want people to understand that living with HIV is not an obstacle. You can live life, go out and have fun, and enjoy a movie date.” Joshua B. Stovall, 37, has been HIV positive 14 years: “I decided to be a part of this photo shoot to show my support of being in care, staying in care, and becoming virally suppressed. The power THE ROLE OF A LIFETIME: LEFT TO RIGHT, TOP ROW: JOSEPH HUTTO, DANIELLE KRUSE, we all possess is to know. Knowing is half ARMANDO RAMIREZ-GUZMAN. MIDDLE ROW: D’EVA LONGORIA, JOSHUA B. STOVALL, the battle. Knowledge is the pursuit of DOUG FERGUSON. BOTTOM ROW: JUDY BROWN, RENÉ GARZA, DUANE CRAMER. happiness.” Danielle Kruse, 48, was diagnosed meds is simply a routine for those of us Garza, 55, who has been positive since with HIV in July 2016: “I was told I had who happen to be HIV positive. My HIV February 2002. “In fact, it’s made me been HIV positive for 12–20 years prior to treatment program is a small part of my make better choices about my diet and my diagnosis. I want to encourage people daily life. Though mundane—like taking a exercise, and take better care of myself. to use PrEP and to get tested. I was a shower, having a meal, or simply going to For me, life goes on.” naïve Iowa girl who never thought I would a movie, it is important.” “Stay positive and learn everything get HIV. Anyone can get it. I took part in For D’Eva Longoria, 43, a heterosexual you can from your doctor and your own this photo shoot to break the stereotype transgender Latina, living life openly rais- research,” offers Joseph Hutto, 35, who of ‘who gets HIV,’ and to erase stigma.” es awareness and combats stigma: “You has been reading POSITIVELY AWARE ever Duane Cramer, 56, has been living are stronger than HIV! It has been almost since he was diagnosed seven years ago. with HIV since 1996; his father passed 10 years since I was diagnosed and I am “Knowledge is power! Use every resource away in 1986 as a result of complica- at the happiest moment of my life!” you can get your hands on to arm yourself tions from HIV/AIDS: “I want to ensure Doug Ferguson, 47, refected on living with information so you can best manage that people who look like me and are like more than half his life with HIV: “When I and maintain your own health and well me—black, same-gender-loving men— frst learned about my HIV status, there being. Live life loudly and proudly!” are always represented in the rainbow were only a couple of medications avail- As the photo shoot neared completion, of those affected by HIV. Black men who able to treat HIV. My frst HIV specialist 67-year-old Judy Brown, HIV positive 26 have sex with men still account for more advised me that I likely had no more than years, looked about the set and observed, than half of newly diagnosed cases of HIV 10 years before I would develop AIDS and “We’ve come a long way, baby!” and those living with HIV. So, for me, it die. I’ve now lived for more than twice —RICK GUASCO is critical that we are visible, vocal, and that time, thanks to advances in treat- open about our status.” ment. I’ve been symptom-free, healthy, THE COVER and additional pictures A noted professional photographer and happy! I even fnished an Ironman from this series were photographed by himself, Cramer commented on the competition in 2012!” John Gress and styled by Wyll Knight, images from the shoot. “A key message “Being HIV positive for over 17 years [__at Pride Arts Center, in Chicago. ] that comes through is that taking HIV has not slowed me down,” says René

4 MARCH + APRIL 2019 | POSITIVELY AWARE 2019 POSITIVELY AWARE HIV DRUG GUIDE OPENING CREDITS

THE PHARMACIST THE DOCTOR THE ACTIVIST THE ASSOCIATE EDITOR THE EDUCATOR

Dr. Eric K. Farmer is an Dr. W. David Hardy Moisés Agosto-Rosario Enid Vázquez has been Carla Blieden, PharmD, HIV clinical pharmacist currently serves as is a longtime treatment Associate Editor of MPH, AAHIVP com- at the Indiana University Adjunct Professor of advocate and educator POSITIVELY AWARE ever pleted her Doctor of Health LifeCare Clinic Medicine at Johns for people living with HIV/ since she joined the mag- Pharmacy, Master of at Methodist Hospital Hopkins University AIDS. A frequent public azine in 1995. She earned Public Health, and in Indianapolis. He School of Medicine and speaker and writer in her B.A. in journalism PGY1 Residency at the was instrumental in lives in Washington, D.C. both English and Spanish, from the University of University of Southern starting formal clinical His previous professional Moisés has played a Wisconsin-Madison. She California. She is certi- pharmacy services in experience includes crucial role in ensuring interned at The Chicago fed as an HIV pharmacist 2009 at LifeCare, one serving as Senior that communities of color Reporter and was a cub and has worked as the of the largest providers Director of Research have equal access to care, reporter for The Hartford clinical pharmacist at of HIV medical services at Whitman-Walker treatment, and lifesaving Courant, the oldest the Maternal, Child, and in the state of Indiana. Health in D.C. (2015- information and has won continuously published Adolescent/Adult Center, At LifeCare, Dr. Farmer 2018), Chief Medical numerous awards for his newspaper in the United a family-centered HIV provides pharmacy Ofcer of Calimmune, work with the HIV com- States. Her freelance clinic in Los Angeles, for services that include a translational science munity. He is currently work has appeared in almost a decade. She medication adherence company investigating the Director of Treatment publications around the works directly with counseling and patient gene-modifed cellular for NMAC (formerly country. She became patients focusing on education, drug informa- therapies as a potential known as the National interested in health adherence to HIV medi- tion services, medication cure for HIV (2013-2015) Minority AIDS Council). reporting because of the cation, managing other procurement, medica- and Director of the Before joining NMAC, he importance it has on chronic diseases, and tion therapy manage- Division of Infectious worked as program man- people’s lives. It is a privi- analyzing HIV medica- ment, and medical care Diseases at Cedars-Sinai ager for the International lege to work on behalf of tion resistance. Carla is coordination services. Medical Center and Treatment Preparedness people living with HIV/ adjunct faculty at USC He currently serves as Professor of Medicine at Coalition (ITPC) with AIDS, Enid says. She School of Pharmacy a clinical preceptor for the David Gefen School the HIV Collaborative believes that HIV is as a where she lectures on APPE students, PGY1 of Medicine at UCLA Fund for HIV Treatment much condition fueled by HIV and her primary residents, and PGY2 (2002-2013). Dr. Hardy Preparedness, a project societal discrimination focus is the integration residents at IU Health has cared for persons of the Tides Foundation. as it is by a virus. As such, of Public Health within and is on the clinical fac- with HIV infection since In this role, he was it makes her reporting the school curriculum. ulty of the Midwest AIDS 1982 and conducted responsible for grant socio-political as well She reviewed the DHHS Training and Education research on HIV and making activities in as medical. She enjoys guidelines and pull-out Center. He is involved in related diseases since Latin America, the reporting on medical drug chart for this guide. the PGY2 ID Residency 1984. Dr Hardy currently Caribbean, and Eastern updates and making Advisory Committee as serves as Chair of the Africa. Previous to them relatable to readers’ well as the Indiana HIV/ Board of Directors of the ITPC he served as the lives. Enid has a special STD Advisory Council HIV Medicine Association Vice President and interest in sexual vio- with the Indiana State (HIVMA) and Chair of the Managing Director for lence and sexual freedom, Department of Health. Dr. Education Committee of Community Access, a and in serving the sex Farmer graduated from the American Academy of Nelson Communications trade worker and trans- Butler University with his HIV Medicine (AAHIVM). Company and member of gender communities. Doctor of Pharmacy in He has worked with the Publicis Healthcare 2007. He then completed several community-based Group. Moisés served as an ASHP-accredited organizations, including the editor of SIDA Ahora, PGY1 pharmacy resi- AIDS Research Alliance, the Spanish publica- dency at Eskenazi Health Alliance for Housing and tion of the People with (formerly Wishard Health Healing, Being Alive- AIDS Coalition of New Services) in Indianapolis, Empowering People with York, and was an active and subsequently an HIV/AIDS, Project Angel member of ACT UP. ASHP-accredited PGY2 Food, and AIDS Project Moisés graduated from HIV specialty pharmacy Los Angeles. the University of Puerto residency at the Center Rico in Rio Piedras with for HIV/AIDS Care and a B.A. in Literature and Research at Boston Education. Medical Center. AGOSTO-ROSARIO BY JONATHAN TIMMES BLIEDEN • BY ISAAC MORA FARMER • AND VÁZQUEZ BY JOHN GRESS

POSITIVELY AWARE | MARCH + APRIL 2019 5 THE CONVERSATION

MIXED EMOTIONS WHILE SUPPLIES LAST! I identiﬁed with your recent Editor’s Note [Jan+Feb 2019]. I turned 80 in November after 30 years of being positive. I have mixed emotions about being JOIN US a long-term survivor because the increasingly painful eﬀects of age-related degenerative diseases are 0 threatening my joy of life. positivelyaware As you pointed out, aging with HIV disease is a process of loss, both of loved ones and of self-image. Even though I consider myself to have lived a productive, successful life, I still @posaware have periods of depression and sadness. The emotional toll of this disease is profound, indeed. Thanks for your work to publish an informative magazine. —JERE ERICKSON [email protected] SAN DIEGO, CALIFORNIA

POSITIVELY AWARE 5537 N. EDUCATING getting copies of these in the BROADWAY ST. past no longer works here, so CHICAGO, IL I am a peer educator here I am reaching out to see if I 60640-1405 at Telford Unit, New Boston, could get connected to the Texas and have been receiv- right person to request some All letters, email, ing your magazines for four drug guides for this year. I online posts, etc. months already (two issues). know I am a bit early still, but are treated as letters to the I just want to say thank you. wanted to start on this now to editor unless I’ve learned a lot of valuable be prepared. otherwise information and our peers —MATT JOHNSON instructed. MINNEAPOLIS, MINNESOTA We reserve the have learned a lot, too. You’re right to edit for doing an awesome job. Your length, style, or hard work is changing lives I’m Melissa Watkins, formerly clarity. Let us here in Telford Unit. Thank of Accordant Health Services, know if you prefer not to have your you once again. and am starting of the new name or city year with a new job with AHF mentioned. NAME WITHHELD in Lithonia, Georgia. I brought NEW BOSTON, TEXAS your wonderful HIV drug chart SUBSCRIPTIONS and posted it. The doctors AND BULK ORDERS GET YOURS NOW here also saw the smaller FOR YOURSELF, Tell us how many tri-fold pocket edition of the copies you want, FOR YOUR ORGANIZATION. where to ship I work at JustUs Health chart, and wanted their own. them, and who (formerly the Minnesota AIDS Now everybody wants one! should get them: Project). We have gotten drug When the 2019 pocket edi- Order additional copies of the distribution@ tpan.com guides from you every year in tion charts roll out, we want 2019 POSITIVELY AWARE the past to help our HIV case those, too! I so appreciate you HIV Drug Guide and managers as well as to put all, and attribute my learning HIV Drug Chart! up in our client rooms. They the meds to your work! have been super helpful and Much love to you, and [email protected] we are interested in getting yours in the mission. more this year. The person —MELISSA WATKINS at our agency responsible for LITHONIA, GEORGIA

© 2019 POSITIVELY AWARE (ISSN: 1523-2883) is published bi-monthly by Test Positive Aware Network (TPAN), 5537 N. Broadway, Chicago, IL 60640. TPAN is an Illinois not-for-profit corporation, providing information and support to anyone concerned with HIV and AIDS issues. POSITIVELY AWARE is a registered trademark of TPAN. All rights reserved. Circulation: 100,000. For reprint permission, email [email protected]. Six issues mailed bulk rate for $30 donation; mailed free to those living with HIV or those unable to contribute.

We accept submission of articles covering medical or personal aspects of HIV/AIDS, and reserve the right to edit or decline submitted articles. When published, the articles become the property of TPAN, POSITIVELY AWARE, and its assigns. You may use your actual name or a pseudonym for publication, but include your name, email address, and phone number with your story. Although POSITIVELY AWARE takes great care to ensure the accuracy of all the information it presents, POSITIVELY AWARE staff and volunteers, TPAN, and the institutions and personnel who provide us with information cannot be held responsible for any damages, direct or consequential, that arise from use of this material or due to errors contained herein. Opinions expressed in POSITIVELY AWARE are not necessarily those of staff or TPAN, its supporters and sponsors, or distributing agencies. THINK GREEN. Information, resources, and advertising in POSITIVELY AWARE do not constitute endorsement or recommendation of any medical treatment or PLEASE RECYCLE product. TPAN recommends that all medical treatments or products be discussed thoroughly and frankly with a licensed and fully HIV-informed THIS MAGAZINE medical practitioner, preferably a personal physician. A model, photographer, or author’s HIV status should not be assumed based on their appearance WHEN FINISHED. in POSITIVELY AWARE, association with TPAN, or contributions to this journal.

6 MARCHMARCH + APRIL 2019 | POSITIVELY AWARE EDITOR’S NOTE JEFF BERRY STOP. LOOK . LISTEN. Instead of hurrying through life, take a moment to breathe

n early September of last year diference in some small way, and how much it I was attending the United States meant to me that she shared her story with me. We exchanged cards, and both went on our busy way, Conference on AIDS in Orlando but I have never forgotten that moment—it will stay and running late for a dinner I had with me for the rest of my life. been invited to that evening. AIDS So this is why we do what we do, why this issue conferences are the endurance you are holding in your hands is so important, and demonstrates the incredible power that knowledge marathons for AIDS activists, from the and sharing our stories can hold. This is our annual Imoment you wake up until you hit your HIV Drug Guide, our 23rd to be exact (I always like pillow late at night you are literally running to point out that there were only three drugs in the from session to meeting to workshop to frst drug guide). It’s not meant to be read from cover to cover, although there is probably that one person reception, just to get up and do it all over out there who does that (thank you!). Rather, glean again. This goes on for a number of days, from it what you will, and keep the issue handy all This is why we and you’re lucky if you get fve to six hours year round for when you need it again. For some that do what we do, of sleep each night. Invariably when you means if you are starting treatment for the frst time, why this issue the DHHS guidelines (“And the Nominess Are...” on you’re holding in get home you are exhausted and spent— page 13) show which regimens are recommended. If your hands is so but in a good way. you are experiencing a side efect, or suspect a drug important, and interaction, go to that section on the drug page to As I was hurrying down a long, wide corridor flled learn more. And if you like looking at pretty pictures demonstrates the with people scurrying to their own reception/dinner/ of pills, the pullout HIV drug chart is just for you! incredible power meeting, one person headed toward me in the oppo- I would be remiss not to thank all of the many that knowledge site direction caught my eye. She seemed to recog- people involved in the making of the drug guide, and sharing our nize me but I was pretty sure I didn’t know her, and I starting with Associate Editor Enid Vázquez and our stories can hold. was late for my dinner, so I smiled back but decided pharmacist Eric Farmer, PharmD, who update the to keep moving. But then as we neared each other bulk of this huge bear (special thanks to Eric for his we both stopped, and she began to talk. And my eyes excellent writing and review); Creative Director Rick started to well up as she shared her story. Guasco, whose fantastic design and amazing covers She introduced herself and said she wanted to continue to blow me away; the talented Dr. W. David thank me. When she was incarcerated (she explained Hardy and Moisés Agosto-Rosario for their expertise then and in a subsequent conversation) they would and insight; Carla Blieden, PharmD, who came out of send her to a local HIV clinic every three months, and the blue to volunteer her help and is now part of the that is where she discovered POSITIVELY AWARE. She team; the mastery and beauty of photographer John told me it gave her hope—I think her exact words Gress; our eagle-eye proofreader Jason Lancaster; were, it saved my life. She told me that reading about with additional thanks to Drew Halbur, BSPharm, and my personal journey and my own struggles touched all of the wonderful people at Walgreens; and the her deeply during a dark time in her life (she had staf of TPAN for putting up with us and our crazi- learned she was HIV positive and had lost a friend ness while we are on deadline. due to complications from AIDS), but by reading the It really does take a village, and it’s important to magazine somehow she knew she was going to be stop and take the time to listen to each other. No okay. She knew nothing about which regimens to one is an island. Individually we can make our own take, or what resources were there for her, but she personal achievements, but collectively and working learned how to formulate questions for her doctor together we can change lives. and get the care that she needed. I told her how glad I was to have made a Take care of yourself, and each other.

@PAeditor PHOTO: JOHN GRESS JOHN PHOTO:

POSITIVELY AWARE | MARCH + APRIL 2019 7 2019 POSITIVELY AWARE HIV DRUG GUIDE INTRODUCTION CLIFFHANGER FOR A CURE Are we ready for a cure for HIV? Of course we are, aren’t we? BY W. DAVID HARDY, MD

A brief history of curing VZV (chicken pox/shingles is a big diference between viral infections in humans virus), CMV (retinitis, colitis), the two viral infections, which EBV (infectious “mono” virus)] makes them very diferent tar- lmost as soon as have been developed to gets for cure—HCV does not HIV was identifed suppress these potentially “integrate” or insert its genetic in 1983 as the cause life- and sight-threatening material into the DNA of of AIDS, the clamor viral infections, but not to human cells that it infects like for a cure for this cure them. HIV does to the human cells Ainsidious viral infection began. The biggest breakthrough which it infects. Eradicating The repeated failures and in truly curing a viral infection non-integrated HCV genes numerous tales of human came only within the last 10 from a human cell is much tragedy that followed gave years with the development easier than the task of cutting rise to a sense of unattainable and approval of many all-oral, out integrated HIV genes from loftiness reserved only for non-interferon-containing, an infected human CD4+ T distant dreams, not reality. single-tablet regimen (STR) cell. When HIV “splices” its This sense of unattainability combination treatments for genetic material into the DNA was shattered in 2007, with hepatitis C (HCV). Currently of human cells, its genes con- the initial reports of Timothy 90–100% of persons with tinue to be carried in those Brown—the Berlin patient— almost any type of HCV, at cells and all “daughter” cells the only person to have ever any stage of liver disease or that come from those cells for been cured of HIV. The door treatment history, with or as long as they live. Thus, the was cracked opened at last; without HIV can be cured challenge of curing an inte- phase, antiretrovirals are no we were on our way. Right? of this infection with 8 to 12 grated viral infection like HIV longer efective against the Maybe not so fast. Let’s weeks of a one-pill-once-a-day is a much higher bar. dormant, integrated virus that take a small dose of real- treatment. The chances of has been spliced into human ity and look carefully at our cured HCV infection coming But wait, what about our CD4+ T cells. It is, in fact, this medical track record for cur- back is very, very low, unless highly efective antiretro- phase of HIV infection that ing viral infections. In 1983, the cured person re-engages viral therapy? Why isn’t it makes up the often spoken modern medicine had rarely in high-risk behavior for enough to cure HIV? about “latent viral reservoir,” ever cured a life-threatening acquiring the infection. which is referring to those viral infection, except per- t’s certainly true that pieces of viral genetic mate- haps herpes simplex (HSV) So, why was HCV so “easy” our current antiretroviral rial quietly sleeping inside of encephalitis (brain infection), to cure and HIV not so? I treatment (ART) is highly human immune cells (CD4+ T initially with the old chemo- efective and has greatly cells), that has the potential to therapy agent vidarabine and irst, it is important to diminished the death and reactivate and produce new later with the more efective point out that HCV destruction that HIV has viruses which can infect new and less toxic acyclovir. But F became curable based waged on humans in many cells. Fortunately, the number even in those cases, the virus upon essential new scientifc parts of the world. But these of these latently infected causing the serious infection, knowledge that came from agents have important cells is small. It is estimated while signifcantly tamped research discoveries on HIV limitations. First, they can that only 1 to 60 per 1 mil- down and put into latency, treatment. The four classes of only work when virus is in its lion CD4+ T cells are latently was still able to recur in the direct-acting agents (DAAs) “actively replicating” phase— infected with HIV. Even surviving person’s future. It that have revolutionized HCV that is, when it is churning though this “1-in-a-milion” or was not eradicated. Since treatment to create a cure are out large numbers of new so number sounds very small, those early days, successful heavily based upon scientifc infectious viruses to travel it is enough to allow HIV to re- suppressive treatments for discoveries about viruses throughout the body to infect emerge in the blood of people many members of the herpes made while scientists were new cells. Second, when virus living with HIV (PLWH) who family of viruses [HSV-1 & -2, studying HIV. Second, there enters its latent, or “sleeping,” stop their HIV medications

10 MARCH + APRIL 2019 | POSITIVELY AWARE after being undetectable for their “Achilles’ heels” to entrance sites that HIV uses Immunologists many, many years. And this attack and stop them from to enter and infect T cells. generally happens within 4 doing harm. We owe a great Finding creative ways to mmunologists will help us to 8 weeks after stopping deal to the virologists for use “gene editing” technol- better understand how we antiretrovirals in most PLWH much of the success of com- ogy to cut out the integrated I can create “new immunity,” on ART. Thus, this is our for- bination ART. HIV genes from the DNA of or resistance against HIV in midable, fnal hurdle between When we think about cur- CD4+ T cells to free them PLWH who did not have that us and a cure for HIV. ing HIV, many tough scientifc from viral control will also be immunity when they frst questions are directed to both one of the virologists’ goals. encountered the virus and Scaling the fnal hurdle of virologists and immunologists. Gene therapy, the science of became infected. In other the latent viral reservoir adding, deleting, or blocking words, they will help us learn Virologists genes within the human DNA, how to retrain or rebuild the IV researchers usu- is still in its infancy for treat- immune systems of PLWH ally fall into two basic he virologists will help us ing human disease; however, to become HIV-resistant with- H camps: the immunolo- better understand and at least one gene therapy has out ART. gists—the scientists who are T discover holes in the way been approved by the FDA With previous serious experts on our incompletely that HIV goes into its latent as treatment for a childhood viral infections, such as polio, understood human immune (or sleeping) phase so that we cancer. small pox, and measles, many system which protects us can use that information to Many of these areas of people became infected but from both foreign invaders shock it awake and attack it, research are already well survived the infection without (infections) and internal lock it in that phase for good, underway; some have shown treatment. This observa- invaders (cancer)—and the or prevent it from going latent promise, others have not and tion told us that the human virologists, those scientists in the frst place. They will dis- are being abandoned, and immune system could be who are experts on every cover ways to protect CD4+ T still others have already “gone re-trained or re-engineered to aspect of how viruses repro- cells from being susceptible back to the drawing board” resist those viruses. duce themselves and cause to HIV; that is, to make them for a second or third revision The ability to “train” the

PHOTO: JOHN GRESS JOHN PHOTO: disease, and then fnding “uninfectable,” by blocking the and re-try. human immune system to

POSITIVELY AWARE | MARCH + APRIL 2019 11 2019 POSITIVELY AWARE HIV DRUG GUIDE INTRODUCTION

Infections are rarely, if ever, truly eradicated from humans. It’s the immune system that is ‘trained’ to do the work. resist viral infections has cells. The slate is wiped clean results in persons with cancer it for a lifetime, or at least become a commonly used of cancer and a new, healthy adequate to explore these many years. Infections are and efective preventative immune system is rebuilt. therapies in PLWH? rarely, if ever, truly eradicated force against viral infections— This is the process that from humans. It’s the immune better known as vaccination Timothy Brown underwent Are we ready for a cure system that is “trained” to do or immunization. In fact, to cure his leukemia, and for HIV? Of course we are, the work. immunization against viral as an added beneft, cured aren’t we? It goes without saying illnesses has been the major him of HIV. However, the that a renewed, reinvigorated, way that we have controlled risk of destroying a person’s growing number of and mutually respectful part- these infections for the last immune system and replac- research publications, nership is needed between 150 years. ing it with a new, cancer-free A from several parts of the PLWH and scientifc/ Unfortunately, there are one is only balanced by the the world, written almost medical communities as we no known human beings who beneft of not dying from an exclusively by PLWH and all embark on our great- have developed long-term, otherwise fatal cancer. The other community advocates, est challenge to date—to natural immunity against HIV. risk-to-beneft ratio of using have documented the PLWH cure HIV. Exceptional, new, So, we do not have a proven stem cell transplantation as a community’s ever vigilant, out-of-the-box thinking and natural pathway to follow cure for both cancer and HIV but hopeful, attitudes, feel- exquisitely refned new takes as we have had with other has been positive, but in only ings, fears, and aspirations on old ideas will be needed as viral infections. (Elite and 1 of over 10 attempts. for a cure for HIV. In addi- the journey unfolds. Voluntary viremic “controllers,” those Is Timothy Brown’s story tion to providing a cogent, altruism, once so evident and PLWH who have undetectable enough to urge other PLWH irreplaceable voice for the proudly practiced in the ear- viral loads or less than 2,000 to take on this risk? Certainly, persons central to this entire lier years of the epidemic, will copies/mL without ART, are if they have lymphoma or leu- discussion, these publications be encouraged and respected. our closest guides to how kemia unresponsive to treat- have refected the need for Carefully worded, clear, and humans can naturally resist ment, but what about PLWH continued frank discussion trusting communication, HIV. Unfortunately, it is esti- without cancer? and education for both the both oral and written, using mated that only 1% to 3% of Another potentially research and PLWH advo- language comfortable for all PLWH fall into the controller promising immune-boosting cacy communities to improve involved will be the order of category.) therapy already approved communication and avoid the day. Borrowing from the How to best create new for cancer treatment and misunderstandings. lessons learned from the immunity for PLWH is going sometimes cure is a new For example, it has days of drug development of to be a challenge the likes of class of medications called been reported that PLWH our currently available ART, which human medicine has immune checkpoint inhibitors prefer the term “eradicat- successful cure strategies will only overcome once before. (ICIs). These human antibody ing” rather than “sterilizing” most likely be given as com- That previous life-saving treat- treatments are aimed at when describing a cure that bination treatments, perhaps ment is for advanced cancers reviving “overstimulated” and will remove all traces of HIV in series, perhaps together. (lymphoma, leukemia) which “exhausted” T cells which from a PLWH’s body. This Unlike those drugs which could not be cured with usual have been turned of by a justifably stems from the are primarily oral and tablet- chemotherapy and radiation natural immune shut-of valve. negative fertility connotations based, cure strategies may therapy. ICIs are designed to block associated with the term well involve more procedures, That treatment is called this turn-of switch, a state “sterilizing”. Further, PLWH intravenous infusions, and stem cell transplantation. It commonly found in T cells in prefer an “eradicating” versus longer periods of follow-up involves taking the youngest, PLWH, and thereby turn the a “functional” cure (ART-free to see if they work. There is freshest cells of the immune immune system back on. remission from HIV without no doubt that the rationale system, called stem cells, Using one’s own revital- all traces of the virus removed for, the desire for, and the from the bone marrow of the ized T cells to fght one’s HIV but rather held in check by understanding of what a same person (for lymphoma) makes good sense, right? new anti-HIV immunity) due cure for HIV means will be or from another person (for While these treatments have to concerns that the virus may diferent and perhaps unique leukemia) and giving them shown promise in many can- return and become resistant to everyone involved, but the to the person with cancer. cers, they can also potentially to ART. From a scientifc/med- common purpose for treading This is done after all cancer cause the immune system to ical standpoint, expectations this uncharted road together (and immune system) cells attack non-HIV-infected cells of a truly eradicating cure may will make it bearable and suc- of that person have been and cause long-term side be too high and unattainable. cessful. destroyed with large doses efects such as low thyroid The best outcome that medi- of chemotherapy and radia- hormone levels, requiring cal science has ever accom- W. DAVID HARDY, MD, is tion therapy. In other words, the afected person to take plished in treating infectious Adjunct Professor of the cancer and the immune thyroid hormone replacement diseases among humans has Medicine, Division of system of the person are frst for life. been to decrease the amount Infectious Diseases at the destroyed and then replaced Here again, are the now of infection to a level that the Johns Hopkins University with healthy new immune proven positive treatment immune system can control School of Medicine.

12 MARCH + APRIL 2019 | POSITIVELY AWARE 2019 POSITIVELY AWARE HIV DRUG GUIDE DHHS HIV TREATMENT GUIDELINES

The category is DHHS guideline recommendations for first-time therapy And the nominees are…

Most people starting HIV treatment That’s according to A pregnancy test should be performed for the frst time (treatment-naïve) should HIV treatment guidelines for those of childbearing potential prior take one of the following: from the U.S. Department of Health to the initiation of INSTI therapy. and Human Services (DHHS). A regimen should be individualized on n Biktarvy Lots of people, however, are not tak- the basis of virologic efcacy (suppres- n Triumeq ing HIV therapy for the frst time; for sion of viral load to less than 50 copies n Tivicay plus Descovy or Truvada example, people who are on therapy and per mL), toxicity, pill burden, dosing n Isentress HD or Isentress, plus Descovy virally suppressed may choose to switch frequency, drug-drug interaction poten- or Truvada to another regimen for improved toler- tial, resistance testing results, comorbid ability or to avoid drug interactions. The conditions (such as kidney disease, In certain clinical (health) situations, guidelines have lots to say about that and hepatitis B or C, etc.), and cost. More frst-time folks may take one of the fol- other situations. details including recommendations for lowing regimens. They are efective and treatment-experienced individuals and tolerable but have some disadvantages A more detailed list those for pregnant women are available when compared with the regimens listed online. Preliminary data have raised con- above or have less supporting data from An antiretroviral (ARV) regimen for a cerns about an increased risk of neural randomized clinical trials. treatment-naïve individual is usually tube defects in infants born to people made up of two nucleoside reverse who were receiving dolutegravir (DTG) at n Symtuza; Prezcobix or Prezista plus transcriptase inhibitors (NRTIs) in the time of conception. Before prescrib- Norvir, with Descovy, Truvada, or combination with a third active ARV ing DTG or another INSTI, refer to Table Epzicom drug from one of three drug classes: an 6b in the guidelines for specifc recom- n Delstrigo; or Pifeltro plus Descovy integrase strand transfer inhibitor (INSTI), mendations on initiating these drugs as n Evotaz or Reyataz plus Norvir, with a non-nucleoside reverse transcriptase part of initial therapy. Descovy, Truvada, or Epzicom inhibitor (NNRTI), or a protease inhibitor AIDSinfo has free mobile applications n Odefsey or Complera (PI) with a pharmacokinetic (PK) that allow access to federally approved n Genvoya or Striblid enhancer (also known as a booster; the HIV/AIDS treatment and research infor- n Atripla; Sustiva plus Descovy; or Symfi two drugs used for this purpose are mation, including a Guidelines mobile or Symfi Lo cobicistat and ritonavir). (See charts app, at aidsinfo.nih.gov/apps.

GRAZVYDAS-ISTOCKPHOTO n Isentress or Isentress HD, plus Epzicom on the following pages.)

POSITIVELY AWARE | MARCH + APRIL 2019 13 2019 POSITIVELY AWARE HIV DRUG GUIDE DHHS HIV TREATMENT GUIDELINES

RATING OF RECOMMENDATIONS 1 A: Strong -". Q\ I I /- B: Moderate Rising to the C: Optional -- MOST PEOPLE STARTING HIV TREATMENT for the RATING OF EVIDENCE / " frst time (treatment naïve) should take one of the following: I I \ \ Biktarvy; Triumeq; Tivicay plus Descovy or Truvada; I: Data from randomized or Isentress HD or Isentress, plus Descovy or Truvada. controlled trials II: Data from well-designed non-randomized trials, observational cohort studies with long-term clinical outcomes, relative bio- availability/bioequivalence Recommended initial regimens for most people with HIV studies, or regimen com- Recommended regimens are those with demonstrated durable virologic parisons from randomized effcacy, favorable tolerability and toxicity profles, and ease of use. switch studies III: Expert opinion INSTI + 2 NRTIs

KEY TO ACRONYMS BIC FTC TAF DTG ABC 3TC 3TC: lamivudine ABC: abacavir Biktarvy Triumeq ART: antiretroviral therapy (BIC/FTC/TAF): (DTG/ABC/3TC) ARV: antiretroviral AI if HLA-B*5701-negative: ATV: atazanavir AI ATV/c: atazanavir/cobicistat ATV/r: atazanavir/ritonavir BIC: bictegravir TAF TAF CD4: CD4 T lymphocyte, or or DTG FTC TDF RAL FTC TDF “T cell” DOR: doravirine .Tivicay.. (DTG) with Isentress. HD.. or Isentress DRV: darunavir Descovy (FTC/TAF) or (RAL) with DRV/c: darunavir/cobicistat Truvada (FTC/TDF): Descovy (FTC/TAF): BII DRV/r: darunavir/ritonavir AI or Truvada (FTC/TDF): BI DTG: dolutegravir EFV: efavirenz EVG: elvitegravir EVG/c: elvitegravir/cobicistat FDA: Food and Drug Recommended initial regimens in certain clinical situations Administration These regimens are effective and tolerable, but have some disadvantages FTC: emtricitabine when compared with the regimens listed above, or have less supporting HLA: human leukocyte data from randomized clinical trials. However, in certain clinical situations, antigen one of these regimens may be preferred. INSTI: integrase strand transfer inhibitor Boosted PI + 2 NRTIs NNRTI: non-nucleoside (In general, boosted DRV is preferred over boosted ATV.) reverse transcriptase inhibitor DRV/c TAF ATV/c TAF DRV/c NRTI: nucleoside reverse or FTC1 or or FTC1 or or ABC 3TC DRV/r TDF ATV/r TDF DRV/r transcriptase inhibitor PI: protease inhibitor Symtuza- (DRV/c/TAF/FTC) .Evotaz.. (ATV/c) or .Prezcobix.. (DRV/c) or RAL: raltegravir or Reyataz + Norvir (ATV/r), Prezista + Norvir (DRV/r), RPV: rilpivirine Prezcobix (DRV/c) or with Descovy (FTC/TAF) or with Epzicom (ABC/3TC) STR: single-tablet regimen Prezista + Norvir (DRV/r), Truvada (FTC/TDF): If HLA-B*5701–negative: TAF: tenofovir alafenamide with Descovy (FTC/TAF) or BI BII TDF: tenofovir disoproxil Truvada (FTC/TDF): fumarate AI

14 MARCH + APRIL 2019 | POSITIVELY AWARE NOTE: THE FOLLOWING ARE AVAILABLE AS CO-FORMULATED DRUGS occasion (NOT A COMPLETE LIST) Epzicom ABC/3TC

Evotaz ATV/c

Biktarvy BIC/FTC/TAF Recommended initial regimens in certain clinical situations Delstrigo DOR/3TC/TDF NNRTI + 2 NRTIs Prezcobix DRV/c 3TC TDF TAF TAF or or or or DOR FTC TAF EFV FTC TDF RPV FTC TDF Symtuza Delstrigo (DOR/TDF/3TC): BI; Atripla (EFV/FTC/TDF): BI; Odefsey (RPV/FTC/TAF) or DRV/c/FTC/TAF or Pifeltro (DOR) with or Sustiva (EFV) + Complera (RPV/FTC/TDF) Descovy (FTC/TAF): BIII Descovy (FTC/TAF): BII; If HIV RNA <100,000 copies/mL Triumeq or Symf (EFV/3TC/TDF): BI and CD4 >200 cells/mm3:BI DTG/ABC/3TC

Symf INSTI + 2 NRTIs: EFV 600 mg/3TC/TDF

TAF or Atripla RAL ABC 3TC EVG/c FTC TDF EFV/FTC/TDF .Isentress.. HD Genvoya (EVG/c/TAF/FTC) or or Isentress (RAL) Stribild (EVG/c/FTC/TDF): Genvoya with Epzicom (ABC/3TC) BI EVG/c/FTC/TAF If HLA-B*5701–negative and HIV RNA < 100,000 copies/mL: CII Stribild EVG/c/FTC/TDF

Odefsey RPV/FTC/TAF Regimens to consider when ABC, TAF, and TDF cannot be used or are not optimal Complera RPV/FTC/TDF

Descovy DTG 3TC DRV/r RAL DRV/r 3TC FTC/TAF

Tivicay (DTG) with Prezista + Norvir (DRV/r) with Prezista + Norvir (DRV/r) Cimduo or Temixys lamivudine•• (3TC): Isentress•• (RAL): with• lamivudine• (3TC) : 3TC/TDF BI If HIV RNA <100,000 copies/mL CI and CD4 >200 cells/mm3: CI Truvada FTC/TDF

FOOTNOTE 1 Lamivudine (3TC) may substitute for emtricitabine (FTC) or vice versa.

NOTES: n Tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) are two forms of tenofovir that are approved by the Food and Drug Administration. TAF has fewer bone and kidney toxicities than TDF, while TDF is associated with lower lipid levels. Safety, cost, and access are among the factors to consider when choosing between the two. n raltegravir (RAL) can be given as RAL 400 mg twice daily or RAL 1200 mg (two 600 mg tablets) once daily.

POSITIVELY AWARE | MARCH + APRIL 2019 15 POSITIVELY AWARE For pagination purposes, this page has been intentionally left blank. ➤

18 MARCH + APRIL 2019 | POSITIVELY AWARE o · -~. •~jl; ,,, .,., ., 2019 POSITIVELY AWARE ~ ;j .. ... ~ ,#, • HIV DRUG GUIDE DRUG INTERACTIONS cf'., ~ :-i ~- • ' ,...,l -~ ·• ~. • · ·• ~ .., . . "' ,.·11t,,'••• .. •• . • I-~•\ .• .. , . • • . j;f .I : .. • ,~; ~ .;•-, .... , A':ft -;_. . ~ ~ '• . • ::...... ,, ~ . ,; ' ·,r\ , .. When• drugs ·• .• . •• ~ . II • ... ~• •• ... • . !'t.l ,I ..... ' . f collide!• ., .. ., ., Understanding, drug interactions • . .• C...... '"

• ,~ I A DRUG INTERACTION is a i ~ .. reaction between two (or more) drugs (called a drug-drug interaction) or between a drug and a food or beverage (called a drug-food interaction). An existing medical condition can make certain drugs potentially harmful (called a drug-condition interaction). For example, For pagination purposes, this page taking a nasal decongestant if you have high blood has been intentionally left blank. pressure may cause an unwanted reaction.

Medicines help us feel efective. Women using hor- n While taking the medicine, ➤ better and stay healthy. But monal contraceptives may should I avoid any other drug interactions can cause need to use an additional or medicines or certain foods problems by reducing or diferent method of birth con- Because of pregnancy- or beverages? increasing the action of a trol to prevent pregnancy. related changes, dosing of medicine or causing adverse an HIV medicine may change n Can I take this medicine (unwanted) side efects. Can drug-food interactions during diferent stages of safely with the other medi- and drug-condition interac- pregnancy. But pregnant cines that I am taking? Are Are drug interactions a tions affect people with HIV? women should always consult there any possible drug problem for people with HIV? with their health care provid- interactions I should know Yes, the use of HIV medicines ers before making any chang- about? What are the signs Treatment with HIV medicines can lead to both drug-food es to their HIV regimens. of those drug interactions? (called antiretroviral therapy interactions and drug-condi- or ART) helps people with HIV tion interactions. How can I avoid n In the case of a drug inter- live longer, healthier lives. But Food or beverages can drug interactions? action, what should I do? drug interactions, especially afect the absorption of some drug-drug interactions, can HIV medicines and increase Tell your health care provider Take medicines according complicate HIV treatment. or reduce the concentra- about all prescription and to your health care provider’s Drug-drug interactions tion of the medicine in the non-prescription medicines instructions. Drug labels between HIV medicines are blood. Depending on the you are taking or plan to take. and package inserts include common, and may reduce or HIV medicine, the change in Also tell your health care important information about increase the concentration concentration may be helpful provider about any vitamins, possible drug interactions. of an HIV medicine in the or harmful. Instructions for nutritional supplements, and Tell your health care provider blood. This can make the HIV medicines afected by herbal products you take. if you have any side efect afected HIV medicine less food specify whether to take that bothers you or that does efective, or increase levels the medicine with or without Before taking a medi- not go away. that also increase the risk of food. (HIV medicines not cine, ask your health care side efects. afected by food can be taken provider or pharmacist these LEARN MORE about drug Drug-drug interactions with or without food.) questions: interactions at aidsinfo.nih. between HIV medicines and Pregnancy is a condition gov/drugs and fda.gov. other medicines may make that can afect how the body n How should I take the

P OS ITIVE LY AWAR E | MARCH + APRIL 2019 19 2019 POSITIVELY AWARE COST SHARING AND HIV DRUG GUIDE PATIENT ASSISTANCE PROGRAMS Supporting role HIV treatment can be costly, but there’s help

Today’s therapies are vastly improved over the Applying for PAPs frst drugs used to treat HIV, but these advance- In 2012, the Department of ments come at a cost. The prices of HIV drugs con- Health and Human Services tinue to rise every year at an average of 7–9 percent. (DHHS), along with seven While in the past these increases usually pharmaceutical companies, haven’t directly afected someone who has the National Alliance of State and Territorial AIDS Directors drug coverage through their health insur- (NASTAD), and community ance plan, increasingly individuals have stakeholders developed a to pay co-insurance (a percentage of the common patient assistance cost of the medication). The good news program application form that can be used by both pro- is that help is out there. State AIDS Drug viders and patients. This com- Assistance Programs (ADAPs), several bines common information non-proft organizations, and the phar- collected on each individual maceutical companies themselves have company’s form to allow indi- programs in place to help you pay for the viduals to fll out just one. Once the form is completed, treatment you need. case managers or individuals then submit the single form A cost-sharing A patient assistance to each individual company, assistance program (CAP, program (PAP) is a program reducing the overall amount also known as a co-pay run through pharmaceutical of paperwork necessary to program) is a program companies to provide free apply for a patient assistance operated by pharmaceuti- or low-cost medications to program. cal companies to ofer people with low incomes In addition to serving as cost-sharing assistance who do not qualify for a special PAP for ADAP wait- (including deductibles, any other insurance or ing list clients, HarborPath co-payments, and co- assistance programs, such operates as a streamlined, insurance) to people with as Medicaid, Medicare, online portal for PAP access. private health insurance or AIDS Drug Assistance HarborPath creates a single to obtain HIV drugs at the Programs (ADAPs). Each place for application and med- pharmacy. Unfortunately individual company has ication fulfllment. This “one many big health insurers diferent eligibility criteria for stop shop” portal provides a have now introduced co-pay application and enrollment streamlined, online process to accumulators to their plans, in their patient assistance qualify individuals and deliver and no longer allow the program. the donated medications of amount of the co-pay cards the participating pharmaceu- to be applied towards their HarborPath, a non-proft tical companies through a deductible or out-of-pocket organization that helps unin- mail-order pharmacy. maximum, or steer them sured individuals living with towards other cost-containing HIV gain access to brand- INFORMATION IN THIS ARTICLE measures such as step name prescription medicines and the following tables is therapy or individual generics at no cost, operates a special adapted from NASTAD’s “HIV that break up an STR. When patient assistance program Pharmaceutical Company HIV choosing your healthcare for individuals on ADAP Patient Assistance Programs plan, make sure your drug is waiting lists. An individual is and Cost-Sharing Assistance covered (on the plan formu- eligible for the HarborPath Programs”: nastad.org/ lary) and know which drug ADAP waiting list program resource/pharmaceutical- tier it is in (your cost for only if he or she has been company-hiv-patient-assis- the drug co-pay is deemed eligible for ADAP in tance-programs-and-cost- based on which his or her state and is verifed sharing-assistance-programs. tier, or category, to be on an ADAP waiting list it falls under). in that state. © CSA-PLASTOCK©

20 MARCH + APRIL 2019 | POSITIVELY AWARE COST-SHARING ASSISTANCE PROGRAMS (CAP)

DRUGS COVERED MANUFACTURER AND CONTACT INFORMATION ASSISTANCE RENEWAL

Kaletra: Co-payment assistance covers AbbVie the frst $400 per prescription per Renews as long as Kaletra and Norvir 800-441-4987, option 4; month. Norvir: Covers up to $1,200 a criteria are met kaletra.com; norvir.com I year for co-payments. Evotaz, Reyataz, and Sustiva: Up to Bristol-Myers Squibb Evotaz, Reyataz, $7,500 annually for co-payments, Automatic 888-281-8981; and Sustiva deductibles, and co-insurance in all renewal bmscustomerconnect.com/bms3assist I commercially-insured plans. Biktarvy, Genvoya, Stribild, and Truvada: Covers the frst $7,200 per year of co-payments. Atripla, Complera Atripla, Biktarvy, and Odefsey: Covers the frst $6,000 Complera, Descovy, Gilead Sciences per year of co-payments. Descovy: Automatic Emtriva, Genvoya, 800-226-2056; Covers the frst $4,800 per year of renewal Odefsey, Stribild, gileadadvancingaccess.com co-payments. Emtriva: Covers the Truvada, and Tybost frst $300 per month/$3,600 per year of co-payments. Tybost: Covers the frst $50 per month/$600 per year of co-payments.

Janssen Therapeutics Covers the frst $7,500 per year Edurant, Intelence, 866-836-0114; of co-payments, deductibles, and Prezista, Prezcobix, edurant.com; intelence.com; co-insurance. Reapply each year and Symtuza prezista.com; prezcobix.com; symtuza.com

Covers the frst $6,800 per year Enrollment Delstrigo, Isentress, Merck and Co. of co-payments, deductibles, and is valid until Isentress HD, 800-444-2080; co-insurance for each of 12 eligible coupon expires, and Pifeltro isentress.com prescriptions. 12/31/2019

Symf and Symf Lo: Covers up to Mylan $6,000 annually in out of pocket Cimduo, Symf, 800-657-6713; expenses for prescriptions for those Reapply each year and Symf Lo cimduo.com; symf.com; symf-lo.com with commercially available insurance. Cimduo: Covers up to $4,800 per year.

Theratechnologies 833-238-4372; Trogarzo Contact program for details trogarzo.com; therapatientsupport.com

Juluca, Lexiva, Juluca, $6,250; Tivicay, $5,000; and Rescriptor, Retrovir, ViiV Healthcare Triumeq, $7,500 per year/per patient Automatic Selzentry, Tivicay, 844-588-3288; maximum. Lexiva, Rescriptor, Retrovir, renewal Triumeq, Trizivir, ViiVconnect.com Selzentry, Trizivir, Viracept, and Ziagen: Viracept, and Ziagen $4,800 per year/per patient maximum.

Maximum beneft is $3,600 per year. Patient Access Network Foundation Invirase Patients may apply for a second grant 866-316-7263; Reapply each year and Viread during their eligibility period subject to panfoundation.org availability of funding.

P OS ITIVE LY AWARE | MARCH + APRIL 2019 21 2019 POSITIVELY AWARE COST SHARING AND HIV DRUG GUIDE PATIENT ASSISTANCE PROGRAMS

PATIENT ASSISTANCE PROGRAMS (PAP)

DRUGS COVERED MANUFACTURER AND CONTACT INFORMATION FINANCIAL ELIGIBILITY

AbbVie 800-222-6885; Kaletra: 500% FPL Kaletra, Norvir kaletra.com; norvir.com (co-pay information Norvir: No income limits only); abbviepaf.org

Boehringer Ingelheim Aptivus, Viramune XR 500% FPL 800-556-8317; bipatientassistance.com

Bristol-Myers Squibb Evotaz, Reyataz, and Sustiva 888-281-8981; 300–500% FPL bmscustomerconnect.com/bms3assist

Atripla, Biktarvy, Complera, Gilead Sciences* Descovy, Emtriva, Genvoya, 800-226-2056; 500% FPL Odefsey, Stribild, Truvada, gileadadvancingaccess.com and Tybost

Edurant, Intelence, Prezista, Janssen Therapeutics 300% FPL Prezcobix, and Symtuza 800-652-6227; jjpaf.org

Merck and Co. Crixivan, Delstrigo, Isentress, 800-727-5400; merckhelps.com; 500% FPL Isentress HD, and Pifeltro delstrigo.com; isentress.com; pifeltro.com

Theratechnologies Trogarzo Call program for details 833-238-4372; trogarzo.com

Combivir, Epivir, Epzicom, Lexiva, ViiV Healthcare Juluca, Rescriptor, Retrovir, 844-588-3288; 500% FPL Selzentry, Tivicay, Triumeq, ViiVconnect.com Trizivir, Viracept, and Ziagen

* Patients who are insured and who do not meet their payer’s coverage criteria are no longer eligible for support via Gilead’s patient assistance program. This includes clients whose insurer has limited access based on: step-therapy or clinical criteria (e.g., drug and alcohol testing).

FOUNDATIONS ADDITIONAL RESOURCES PROVIDING ACCESS TO CARE ASSISTANCE THESE MAY BE OF INTEREST TO INDIVIDUALS LIVING WITH HIV FOR PEOPLE LIVING WITH HIV Harbor Path Clinical Trials Health Insurance Marketplace harborpath.org clinicaltrials.gov healthcare.gov Provides access to free medications for uninsured A service of the U.S. The ofcial site of the Health people living with chronic illnesses; administers National Institutes of Health, Insurance Marketplace, AIDS Drug Assistance Program (ADAP) Waiting ClinicalTrials.gov is a registry Healthcare.gov allows individu- List Program. and results database of publicly als and families to sign up for and privately supported clinical insurance coverage through the PAN Foundation studies of human participants Afordable Care Act. panfoundation.org conducted around the world. (866) 316-7263 Treatment Action Group Provides necessary healthcare treatments to the Fair Pricing Coalition (FPC) treatmentactiongroup.org underinsured population. fairpricingcoalition.org Treatment Action Group As part of their advocacy work, collaborates with activists, Patient Advocate Foundation the Fair Pricing Coalition (FPC) community members, patientadvocate.org negotiates with companies to scientists, governments, and (800) 532-5274 ensure that cost-sharing and drug companies to ensure Provides arbitration, mediation, and negotiation patient assistance programs that all people with HIV, TB, services to settle issues with access to care, are adequately generous and or HCV receive lifesaving medical debt, and job retention related to illness. easy to apply for. treatment, care, and information.

22 MARCH + APRIL 2019 | POSITIVELY AWARE 2019 POSITIVELY AWARE HIV DRUG GUIDE NEXT STEPS On with the show! Moving beyond your diagnosis—fnding a provider, knowing your rights, and more

HIV treatment Insurance HIV prevention It’s recommended that everyone Just because you have health insur- When you are on efective antiretroviral treat- with HIV be on antiviral therapy. It’s ance doesn’t mean that treatment ment (ART) and your virus is undetectable (less been shown that with early treat- is free. There are co-pays and other than 200 copies) for at least six months, it also ment, people living with HIV will live a costs for medical care. (See the cost- means you can’t transmit HIV to your partner near-normal lifespan. Treatment also sharing and medication assistance (Undetectable equals Untransmittable, or U=U). prevents transmission of the virus. charts beginning on page 21.) For This is also called “treatment as prevention,” those without insurance, check with or TasP. your state’s AIDS Drug Assistance Pre-exposure prophylaxis (PrEP) is when Find an HIV specialist Program (ADAP), or go to healthcare. people vulnerable to HIV take medicine to lower It’s good to fnd a medical provider gov, or call (800) 318-2596. their chance of acquiring HIV. Currently Truvada who treats other people with HIV, is the only drug approved for PrEP. Daily PrEP or is knowledgable about treating reduces the risk of acquiring HIV from sex by HIV; look for an HIV specialist. The HIV and the ADA nearly 100%. Among people who inject drugs, it American Academy of HIV Medicine How are people with HIV protected by reduces the risk by more than 70%. and the HIV Medicine Association the nation’s disability law? Read the PEP (post-exposure prophylaxis) means tak- each have a provider fnder. Go to section on HIV from the Americans ing antiretroviral medicines (ART) after being hivma.org and aahivm.org. In addition, with Disabilities Act at ada.gov/ potentially exposed to HIV to prevent acquiring your local AIDS service organization archive/hivqanda.txt. HIV. PEP should be used only in emergency knows the HIV specialists in your situations and must be started within 72 hours area, and can help point you in the after a recent possible exposure to HIV. If you right direction. HIV anti-discrimination law think you’ve recently been exposed to HIV dur- The National Center for HIV Law ing sex, or through sharing needles and works and Policy advocates for the rights to prepare drugs, or if you’ve been sexually Medical care of people living with HIV and covers assaulted, talk to your health care provider or Ideally, people with HIV should have several areas of concern (such an emergency room medical provider about a CD4+ T cell count and HIV viral as employment, housing, and PEP right away. load measured every three to four immigration). Its website includes a Sexually transmitted diseases (STIs) are months following suppression of HIV link to organizations, by state, that infections that spread from person to person viral load with the use of efective can provide legal information to through sexual contact, including anal, vaginal, antiretroviral therapy (ART). Testing people living with HIV. Write the or oral sex. HIV is an STI, but TasP, PrEP, and every six months and even annually center: 65 Broadway, Suite 832, New PEP do not prevent transmission of other STIs may be acceptable once your virus is York, NY 10006. Call (212) 430-6733. such as gonorrhea or syphilis. undetectable for an extended period Go to hivlawandpolicy.org. Having HIV and another STI may increase of time and you are in general good the risk of HIV transmission. Condoms and health. other methods can help prevent or lower your risk for STIs. People with HIV should get tested n The T-cell count is a measure of for STIs at least once every year if they are immune function. sexually active, and more often depending on n Viral load is a measure of how individual risk factors or symptoms. much virus is in your blood. n Generally, the viral load test result is given greater weight.

Baseline At diagnosis or soon thereafter and before starting treatment, your clinic should check you for: n Other STIs n HIV drug resistance n Hepatitis B and C ©SUBJUG-ISTOCKPHOTO

P OS ITIVE LY AWARE | MARCH + APRIL 2019 23 2019 POSITIVELY AWARE HIV DRUG GUIDE HOW TO USE THIS GUIDE

Your map to the stars Getting the most out of your drug guide

Below are tips to help you and your care providers make empowered, Talking to your doctor informed treatment decisions. Medications included in the 2019 You can play an active role in your health care by talking to your doctor. Clear and HIV Drug Guide are those most commonly used, or expected to be honest communication between you and approved in the coming year. your physician can help you both make smart choices about your health. It’s With so many choices out there, we Prezcobix (darunavir/cobicistat). A single- important to be honest and upfront about order the drug pages by those that are tablet regimen (STR) contains drugs your symptoms even if you feel embar- the best options and list them frst, fol- from diferent classes and is a complete rassed or shy. Have an open dialogue lowed by commonly prescribed drugs in regimen in one pill, such as Biktarvy with your doctor—ask questions to make each category. To quickly fnd your drug, (bictegravir/emtricitabine/tenofovir sure you understand your diagnosis and go to the next page. On the pullout chart, alafenamide). treatment. drugs are listed by category and then Anti-HIV drugs should always be Here are a few tips that can help you alphabetically. Older drugs that are rarely taken in combination using two or more talk to your doctor and make the most of used are only pictured (without dosing drug classes (for example, an integrase your appointment: information) at the bottom of the pullout inhibitor plus two nukes). Single-tablet n Write down a list of questions and con- chart. regimens (STRs) are in their own cat- cerns before your appointment. egory, and combine multiple classes of n Consider bringing a close friend or Goal of HIV therapy drugs into one tablet. STRs are widely family member with you. Understanding HIV treatment is the used for frst-time treatment and for their n Take notes about what the doctor says, key to success. The goal of therapy is to convenience, but they are not for every- or ask a friend or family member to suppress the virus to an undetectable body, including some people who are take notes for you. level (meaning the virus in your blood is treatment-experienced or have multi-drug n Learn how to access your medical so low, it cannot be detected by normal resistance. records, so you can keep track of test tests). This will keep you healthy, and results, diagnoses, treatments plans, the sooner you start therapy, the less Recommendations for use and medications and prepare for your damage to your immune system so you’ll The Department of Health and Human next appointment. stay healthier, longer. When you are on Services (DHHS) and the International n Ask for the doctor’s contact informa- efective antiretroviral treatment (ART) AIDS Society-USA (IAS-USA) both tion and their preferred method of and undetectable (less than 200 copies) publish recommendations for the communication. for at least six months, it also means you use of HIV antiretroviral drugs. We n Remember that nurses and phar- can’t transmit HIV to your partner (unde- include information on some of the macists are also good sources of tectable equal untransmittable, or U=U). recommendations on page 13, and at information. Getting to and staying undetectable the top of each drug page, as well as means you need to take your medication in the pullout drug chart. DHHS and More information online as prescribed (for example, if it’s with or IAS-USA guidelines are very similar, but Operated by the National Institutes of without food), and not miss doses. for consistency we reference only the Health, AIDSinfo maintains factsheets on DHHS guidelines. For complete guideline each HIV medication at aidsinfo.nih.gov/ Drug names recommendations go to aidsinfo.nih.gov understanding-hiv-aids/fact-sheets/21/58/ When a drug is in development it’s frst or iasusa.org/resources/guidelines. fda-approved-hiv-medicines. Download given a “generic” or “scientifc” name iPhone and Android apps that provide (such as dolutegravir). At medical confer- Drug pricing and access drug info, treatment guidelines, and ences and in scientifc publications you The Average Wholesale Price (AWP) is a glossary: aidsinfo.nih.gov/apps. You will often see three-character abbrevia- listed on each drug page and is a way to can also fnd the online version of your tions used (DTG). Once it’s approved, it’s compare costs of drugs. It is not what you medication’s drug page from our HIV given its brand name (Tivicay), which would pay if you were to pay the full retail Drug Guide by adding your drug’s name most people know it by. price. In the drug cost-sharing and patient after typing positivelyaware.com into your assistance program charts (beginning on browser (for example, positivelyaware. Drug classes and co-formulations page 21) we include information on how com/triumeq). A fxed-dose combination (FDC) combines to access programs that can help cover all two or more drugs in one tablet, such as or part of the costs of these medications.

26 MARCH + APRIL 2019 | POSITIVELY AWARE 2019 POSITIVELY AWARE HIV DRUG GUIDE INDEX

In this guide, HIV drugs are grouped into eight categories— plus, one additional category for select non-HIV drugs. Places! More information is available at positivelyaware.com

STR LA INSTI PI PKE NRTI NNRTI Ei/AI

SINGLE-TABLET LONG-ACTING INTEGRASE STRAND PROTEASE PHARMACOKINETIC NUCLEOSIDE NON-NUCLEOSIDE ENTRY INHIBITOR/ REGIMEN INJECTABLE TRANSFER INHIBITOR INHIBITOR ENHANCER REVERSE REVERSE ATTACHMENT (MULTIPLE• •REGIMEN (INTEGRASE• INHIBITOR) • (BOOSTER)• TRANSCRIPTASE• TRANSCRIPTASE• INHIBITOR• DRUG CLASSES) INHIBITOR INHIBITOR (“NUKE”) (“NON-NUKE”)

PAGE BRAND NAME CATEGORY GENERIC NAME 38 Atripla STR efavirenz/emtricitabine/tenofovir DF (EFV/FTC/TDF) 28 Biktarvy STR bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) 51 Cimduo NRTI * lamivudine/tenofovir DF (3TC/TDF) 37 Complera STR rilpivirine/emtricitabine/tenofovir DF (RPV/FTC/TDF ) 32 Delstrigo STR doravirine/lamivudine/tenofovir DF (DOR/3TC/TDF) 49 Descovy NRTI * emtricitabine/tenofovir alafenamide (FTC/TAF) 57 Edurant NNRTI rilpivirine (RPV) 53 Emtriva NRTI emtricitabine (FTC) 54 Epivir NRTI lamivudine (3TC) 52 Epzicom NRTI * abacavir/lamivudine (ABC/3TC) 45 Evotaz PI / PKE atazanavir/cobicistat (ATV/COBI) 34 Genvoya STR elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (EVG/COBI/FTC/TAF) 60 Intelence NNRTI etravirine (ETR) 42 Isentress HD INSTI raltegravir (RAL) 30 Juluca STR dolutegravir/rilpivirine (DTG/RPV) 47 Norvir PKE ritonavir (RTV) 36 Odefsey STR rilpivirine/emtricitabine/tenofovir alafenamide (RPV/FTC/TAF) 58 Pifeltro NNRTI doravirine (DOR) 43 Prezcobix PI / PKE darunavir/cobicistat (DRV/COBI) 44 Prezista PI darunavir (DRV) 46 Reyataz PI atazanavir sulfate (ATV) 61 Selzentry EI maraviroc (MVC) 35 Stribild STR elvitegravir/cobicistat/emtricitabine/tenofovir DF (EVG/COBI/FTC/TDF) 59 Sustiva NNRTI efavirenz (EFV) 39 Symf/Symf Lo STR efavirenz/lamivudine/tenofovir DF (EFV//3TC/TDF) 31 Symtuza STR darunavir/cobicistat/emtricitabine/tenofovir alafenamide (DRV/COBI/FTC/TAF) 41 Tivicay INSTI dolutegravir (DTG) 29 Triumeq STR dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) 62 Trogarzo AI ibalizumab-uiyk (IBA) 50 Truvada NRTI * emtricitabine/tenofovir DF (FTC/TDF) 48 Tybost PKE cobicistat (COBI) 55 Viread NRTI tenofovir disoproxil fumarate (tenofovir DF, or TDF) 56 Ziagen NRTI abacavir sulfate (ABC) * Fixed-dose combination of two drugs from the same drug class.

HIV DRUGS EXPECTED TO BE APPROVED IN 2019 ...... 40 Brand name TBD ..■LA ...... injectable long-acting cabotegravir/rilpivirine (CAB LA/RPV LA) 33 Brand name TBD STR dolutegravir/lamivudine (DTG/3TC) 63 Brand name TBD •AI fostemsavir (FTR) HIV PREVENTION 68 Truvada for PrEP PrEP emtricitabine/tenofovir DF (FTC/TDF) NON-HIV DRUGS - 66 Egrifta tesamorelin for injection for HIV-related excess belly fat 66 Mytesi crofelemer for HIV/AIDS-associated diarrhea 67 Serostim somatropin for injection for HIV-related wasting

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POSITIVELY AWARE | MARCH + APRIL 2019 27 2019 POSITIVELY AWARE HIV DRUG GUIDE

Biktarvy bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) SINGLE-TABLET REGIMEN CONTAINING RECOMMENDED INITIAL REGIMEN STR AN INSTI AND TWO NRTIs ★ FOR MOST PEOPLE n STANDARD DOSE • antiretroviral drug, in this DR. DAVID HARDY SAYS: Biktarvy became the One tablet once daily without regard to food. Tablet case bictegravir, does not eighth STR approved by the FDA, in February contains 50 mg of the INSTI bictegravir plus 200 mg require another medication 2018. Many consider this three-drug, unboosted, inte- emtricitabine and 25 mg tenofovir alafenamide (TAF). such as Norvir or cobicistat grase inhibitor-containing (bictegravir) and TAF- to increase its drug levels in containing STR to be a crowning achievement of Take missed dose as soon as possible, unless it is the body.) This is a really big many years of HIV drug development. But is it any closer to the time of your next dose. Do not double up on deal due to less drug interac- better than other ART regimens? Based on the clini- your next dose. Biktarvy is not recommended for people tions when there’s no boost- cal trial data, it is difficult to see distinct advantages with CrCl less than 30 mL/min or people with severe liver ing. Biktarvy is the second of Biktarvy over Triumeq or Tivicay + Descovy or any impairment. smallest INSTI-based STR clear advantage of switching from a suppressive and tablet, which may help well-tolerated, boosted protease inhibitor or some individuals who have Triumeq—other than reducing the number of pills in ➤ SEE ALSO DESCOVY, the anti-arrhythmic dofeti- difficulty swallowing pills. an ART regimen or persistent nausea or other PLWH- which is contained in lide, or St. John’s wort. Not Pediatric study is ongoing. reported side effects. One possible advantage of this drug (bictegravir is recommended to be taken New preliminary data from Biktarvy over Triumeq could be its use as a first-line not available separately). with Epivir-HBV, Hepsera, an observational study in ART regimen in same-day or rapid ART start pro- ➤ SEE PACKAGE INSERT for or Vemlidy, all three for Botswana suggest that grams due to the requirement for HLA-B*5701 testing more complete informa- treatment of hepatitis B. there may be an increased for Triumeq. Data from two clinical trials (GS 380- tion on potential side Biktarvy should be taken risk of birth defects in 1489 and 1490) comparing Biktarvy to Triumeq or to effects and interactions. two hours before taking infants born to those who Tivicay plus Descovy showed very high and very close laxatives or antacids, the were receiving dolutegravir, (92% vs. 93% and 89% vs. 93%, respectively) rates of n POTENTIAL SIDE EFFECTS ulcer medication sucralfate, which is chemically similar undetectable viral loads among PLWH receiving their AND TOXICITY oral iron or calcium supple- to bictegravir, at the time first ART regimen after one year of treatment. The Most common side effects ments (but these two can be of conception. Consult your conclusion from each study was that Biktarvy was as observed in study partici- used with Biktarvy if taken provider to discuss guidance good as or similar to Triumeq or Tivicay plus Descovy. pants include nausea (5%), together with food), or buff- on how to manage regimens Although there was more mild to moderate nausea headache (5%), and diar- ered medications. Start met- containing an INSTI if there reported by PLWH receiving Triumeq versus those rhea (6%). Five individuals formin at lowest dose and is any possibility of concep- receiving Biktarvy, only 1 out of 315 PLWH stopped in Study 1490 and none titrate based on glycemic tion. At this time, the use of Triumeq due to nausea. The two-year follow-up of in Study 1489 stopped control. Monitor for metfor- Biktarvy is not recommend- both of these studies continued to show high and Biktarvy due to side effects, min adverse effects. When ed during pregnancy due to similar rates of undetectable viral loads (87.9% vs. none of which were due to starting or stopping Biktarvy lack of published data in 89.8% and 84.1% vs. 86.5%, respectively) and no new kidney problems. Serum in people on metformin, pregnant women. differentiating characteristics between the regimens. creatinine, estimated cre- dose adjustment of metfor- Two clinical trials have studied the use of Biktarvy as atinine clearance, urine min may be necessary to n MANUFACTURER a switch ART regimen for PLWH with undetectable glucose, and urine protein maintain optimal glycemic Gilead Sciences, Inc viral loads receiving a boosted protease inhibitor regi- should be obtained before control. Can be taken with gilead.com men (Prezista + Norvir or Tybost, or Reyataz + Norvir initiating Biktarvy and the hepatitis C medications biktarvy.com or Tybost; GS 380-1878) or Triumeq (GS 380-1844). should be monitored during Epclusa, Harvoni, Sovaldi, (800) GILEAD-5 The one-year results of these studies showed that the therapy. There have been and Vosevi. Not intended (445–3235) PLWH who switched to Biktarvy and those who rare reports of depres- to be taken with other HIV remained on their initial regimens both had excellent sion and suicidal ideation, medications, unless pre- n AVERAGE WHOLESALE PRICE and similar results (1878: 92% vs. 89% and 1844: 94% primarily in patients with scribed that way. $3,534.78/month vs. 95%) in terms of maintained undetectable viral a history of psychiatric ill- Tell your provider or loads and minimal side effects with both regimens. nesses, in people receiving pharmacist about all Of note, in the 1844 study, a decrease in nausea was INSTI-based regimens. The medications, herbals, and reported in the PLWH who switched to Biktarvy. In all DHHS guidelines recom- supplements you are tak- of these clinical trials studying Biktarvy, there were mend closely monitoring ing or thinking of taking, few PLWH who experienced virologic failure and patients with pre-existing prescribed or not, as there when they did, their re-emerging HIV did not show psychiatric conditions on are other drug interactions any evidence of integrase inhibitor resistance—a an INSTI. Prior to initiation, which are not listed here. finding very similar to Tivicay and Triumeq. To date, people should be tested for no emergent integrase resistance to Biktarvy has hepatitis B (HBV) infec- n MORE INFORMATION been reported in clinical practice. tion. Severe exacerbations Received FDA approval in of hepatitis B have been February 2018. Biktarvy is ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: reported in people who are quickly becoming a top dog 0 Bikarvy is a good option for those recently co-infected with hepatitis B in HIV treatment. The data infected and treatment virgins and those treatment- and have discontinued the show that the bictegravir experienced that are facing difficulties with their emtricitabine and/or teno- drug resistance barrier is current treatment regimen. As with any drug, there fovir components. Monitor comparable to that of dolute- are side effects and drug interactions to be aware of liver enzymes closely in gravir and protease inhibi- by both the patient and the doctor. For example, you people co-infected with tors (like Prezista). That is should not take Biktarvy if you take dofetilide to treat hepatitis B and, if appro- a huge advantage. Biktarvy irregular heartbeat; it could be serious and possibly priate, initiation of anti- is the first unboosted INSTI- fatal. Avoid rifampin, which is used to treat some hepatitis B therapy may be containing STR with TAF, bacterial infections like tuberculosis. In general warranted. and the second unboosted Biktarvy is well tolerated and is very effective. INSTI STR overall (the other n POTENTIAL DRUG INTERACTIONS is Triumeq). (“Unboosted” Do not take with rifampin, means that the primary

28 M A R CH + A P RIL 201 9 POSITIVELY AWARE positivelyaware.com/biktarvy 2019 POSITIVELY AWARE HIV DRUG GUIDE

Triumeq dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) SINGLE-TABLET REGIMEN CONTAINING RECOMMENDED INITIAL REGIMEN STR AN INSTI AND TWO NRTIs ★ FOR MOST PEOPLE IF HLA-B*5701 NEGATIVE n STANDARD DOSE • taken with other HIV medi- DR. DAVID HARDY SAYS: Triumeq was the fourth One tablet once daily, without regard to food, for people cations, unless prescribed STR approved, in 2014, the second STR contain- with no evidence of INSTI resistance. An additional that way. Tell your provider ing an integrase inhibitor (without a booster), and the 50 mg dose of dolutegravir (brand name Tivicay) or pharmacist about all first STR with Ziagen/Epivir instead of Viread/Emtriva. separated by 12 hours from Triumeq is required for medications, herbals, and In three of four initial studies in PLWH starting their people who have INSTI drug resistance or are taking supplements you are tak- first ART regimen (including one study for women certain other medications. Tablet contains 50 mg ing or thinking of taking, only) comparing Triumeq to either Sustiva, Prezista/ of the INSTI dolutegravir plus 600 mg abacavir and prescribed or not, as there Norvir, Reyataz/Norvir, or Isentress, Triumeq was 300 mg lamivudine. are other drug interactions shown to be superior to (better than) the comparison which are not listed here. ART regimen (Atripla, Prezista/Norvir, and Reyataz/ For adults and children weighing at least 88 pounds Norvir) and similar to the other integrase inhibitor- (40 kg). Take missed dose as soon as possible, unless it n MORE INFORMATION containing ART regimen (Isentress). These results is closer to the time of your next dose. Do not double up Triumeq is the only single- were strengthened by the finding that in all of these on your next dose. Dose cannot be adjusted for people tablet regimen (STR) that studies, no HIV resistance (viral mutations) was found with kidney or liver problems. Triumeq should not be used contains Epzicom as the when a PLWH’s viral load did not respond, or stopped in people with CrCl less than 50 mL/min or moderate or NRTI backbone. Compared responding, to Triumeq and their viral load became severe liver impairment. to other INSTIs, dolutegravir detectable. This was a new and unique finding for has a relatively high genetic Triumeq compared to other integrase inhibitor-con- barrier against the develop- taining ART regimens (Stribild, Genvoya, and ➤ SEE THE INDIVIDUAL co-pay chart). Read more ment of drug resistance, Isentress). In clinical trials, side effects seen with DRUGS CONTAINED IN about HSR online. Prior to similar to the protease Triumeq have been uncommon and rarely a reason TRIUMEQ: Tivicay, Ziagen, initiation, people should inhibitors (such as Prezista). for PLWH to stop their treatment. HIV drug resistance and Epivir. be tested for hepatitis B In addition, dolutegravir- associated with Triumeq has been seen in clinical ➤ SEE PACKAGE INSERT for (HBV) infection. Severe containing regimens have practice in a handful of oftentimes poorly or incom- more complete informa- exacerbations of hepatitis demonstrated virologic pletely documented anecdotal cases since its approv- tion on potential side B have been reported in superiority over Prezista- al. Recently, the use of dolutegravir in HIV-positive effects and interactions. people who are co-infected containing regimens. women who desire to become pregnant or who could with hepatitis B and have Triumeq has relatively few become pregnant without contraception has been n POTENTIAL SIDE EFFECTS discontinued the lamivudine drug interactions and is well strongly discouraged by many international and AND TOXICITY component. Monitor liver tolerated. Triumeq does not national regulatory and advisory organizations (WHO, Triumeq is generally well enzymes closely in people cover HBV as well as other DHHS/FDA, IAS-USA, EACS) due to the unexpected tolerated. The most com- co-infected with hepatitis STRs and therefore requires observation of an increased incidence of neural tube mon side effects that B and, if appropriate, ini- another anti-HBV medica- defects (serious birth defects affecting a baby’s neu- occurred in 2–3% of study tiation of anti-hepatitis B tion in addition to its lamivu- rologic system) seen among HIV-positive women subjects are insomnia, therapy may be warranted. dine component. Triumeq is receiving dolutegravir at the time of conception in headache, and fatigue. See “More Information.” a relatively large STR tablet, Botswana in a preliminary review of the Tsepamo Dolutegravir can cause a which can potentially be an study. Final results of the study will be reported later small, reversible increase in n POTENTIAL DRUG INTERACTIONS issue for individuals who in 2019. Of note, these birth defects have not been serum creatinine within the Do not take with the have difficulty swallow- seen in women who start dolutegravir in the second first few weeks of treatment anti-arrhythmic dofetilide. ing. Another STR contain- or third trimester of pregnancy. Some HIV-treating without affecting actual Triumeq should be taken ing dolutegravir is Juluca. medical care providers and PLWH have avoided kidney function. There have two hours before or six New preliminary data from Triumeq due to reports of an increased risk of heart been rare reports of depres- hours after taking antac- an observational study in attacks with Ziagen, one of the medications in sion and suicidal ideation, ids or laxatives, the ulcer Botswana suggest that there Triumeq. This sometimes limits the use of Triumeq. In primarily in patients with medication Carafate, iron may be an increased risk of addition, it is strongly encouraged that PLWH have a a history of psychiatric ill- or calcium supplements, birth defects in infants born blood test to look for a genetic marker (HLA-B*5701) nesses, in people receiving or buffered medications. to those who were receiv- that is associated with a serious allergic reaction to INSTI-based regimens. The Triumeq can be taken ing dolutegravir at the time the Ziagen. If the marker is present, no ART regimen DHHS guidelines recom- together with iron- or calci- of conception. Until more with Ziagen should be used. Triumeq has been and mend closely monitoring um-containing supplements information is available, reg- continues to be a recommended first-line ART regi- patients with pre-existing if taken with food. Other imens containing dolutegra- men since its approval in both DHHS and IAS-USA psychiatric conditions on an acid reducers/heartburn vir are not recommended for guidelines. An increasing, but still small, number of INSTI. Conflicting data sug- medications (e.g., Aciphex, use in ART-naïve patients reports have noted increased cases of insomnia, gest a potential risk for heart Dexilant, Prilosec, Pepcid, who are pregnant and with- mental stimulation, and worsening of mental health problems when using aba- Zantac, Prevacid) are okay in 12 weeks of conception. problems associated with Triumeq. cavir-containing regimens in to use. Avoid co-adminis- Consult your provider to people with high risk for car- tration with oxcarbazepine, discuss guidance on how to ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: diovascular disease. Monitor phenobarbital, phenytoin, manage regimens contain- 0 Make sure your doctor monitors your kidney for signs of hypersensitivity or St. John’s wort. Start ing dolutegravir if there is function as well your heart. Abacavir has been associ- reaction (HSR) to abacavir. metformin at lowest dose any possibility of conception. ated with cardiovascular disease and a serious aller- Prior to starting Triumeq, and titrate based on gly- gic reaction for which the drug must be discontinued all individuals should be cemic control. Monitor for n MANUFACTURER immediately and never taken again. It’s important to given a blood test for HLA- metformin adverse effects. ViiV Healthcare make sure you are not predisposed to this hypersen- B*5701 (a genetic marker) Avoid use of sorbitol- viivhealthcare.com sitivity reaction seen with abacavir. There is a blood to identify patients at risk containing medicines with triumeq.com test that can predict predisposition to it. for this reaction. This test lamivudine; there are many, (877) 844-8872 is covered by most insur- such as acetaminophen ance and by LabCorp/ViiV liquid (Tylenol liquid and n AVERAGE WHOLESALE PRICE (see company contact on others). Not intended to be $3,467.23/month positivelyaware.com/triumeq POSITIVELY AWARE M A R CH + A P RIL 201 9 29 2019 POSITIVELY AWARE HIV DRUG GUIDE

Juluca dolutegravir/rilpivirine (DTG/RPV) STR SINGLE-TABLET REGIMEN CONTAINING RECOMMENDED AS CONTINUATION THERAPY FOR PEOPLE AN INSTI AND AN NNRTI ★ WITH UNDETECTABLE HIV VIRAL LOAD FOR AT LEAST 6 MONTHS n STANDARD DOSE • medications, herbals, and DR. DAVID HARDY SAYS: Juluca, the seventh One tablet once daily, with a meal (see Edurant), for supplements you are tak- STR approved by the FDA, in late 2017, is a adults who are virologically suppressed (have an ing or thinking of taking, departure from the six previous STRs. This is because undetectable viral load of less than 50 copies per mL) prescribed or not, as there instead of being approved for initial treatment of on a current ART (antiretroviral therapy) regimen for at are other drug interactions PLWH and/or for use as a “switch regimen,” Juluca is least 6 months and who have no history of treatment which are not listed here. specifically and only approved as a “switch regimen” failure or resistance mutations associated with in PLWH with undetectable viral loads and no previ- rilpivirine or dolutegravir. Tablet contains 50 mg of the n MORE INFORMATION ous history of failed ART regimens. Juluca is also the INSTI dolutegravir plus 25 mg of the NNRTI rilpivirine. Juluca is the first two-drug first two-drug, instead of a three-drug, STR. What, combination approved as a you may ask, is the idea behind using only two drugs Take missed dose as soon as possible, with a meal, complete regimen for HIV. to keep HIV suppressed rather than the usual three unless it is closer to the time of your next dose. Do not It replaces a three- or four- drugs? The approval of Juluca as a two-drug “mainte- double up on your next dose. For proper absorption, drug therapy for people with nance” ART regimen is unique and follows on the rilpivirine must be taken with a meal that you chew— undetectable viral loads results of two large Phase 3 studies (SWORD 1 & 2) not just nutritional drinks or protein shakes. who want to switch to a which enrolled more than 1,000 PLWH with undetect- simpler or smaller tablet able viral loads receiving an NNRTI-, boosted PI-, or regimen. People switching integrase inhibitor-containing ART regimen and no ➤ SEE THE INDIVIDUAL of birth defects—see “More to Juluca must be virologi- previous failed ART regimens. Half of the PLWH were DRUGS CONTAINED IN information.” cally suppressed (with viral switched to Juluca, the other half remained on their JULUCA: Tivicay and loads of less than 50 copies previous ART regimen. Ninety-five percent of both Edurant. n POTENTIAL DRUG INTERACTIONS per mL) on a stable antiret- groups of PLWH maintained undetectable viral loads ➤ SEE PACKAGE INSERT Do not take Juluca with roviral regimen for at least a year later; 89% of those switched initially main- for more complete the anti-arrhythmic dofeti- six months. This is a new tained their undetectable viral loads two years later. information on potential lide. If taking rifabutin, add HIV treatment strategy and More PLWH receiving Juluca reported side effects side effects and an Edurant tablet to Juluca potentially a game changer, and stopped taking Juluca than those PLWH who interactions. dose. If you take antacids, especially with other dual- stayed on their previous ART regimens, but no new or laxatives, or other products drug antiviral medications unexpected side effects were reported. The use of n POTENTIAL SIDE EFFECTS that contain aluminum, on the way. Those able Juluca has shown a slow but steady rise since its AND TOXICITY calcium carbonate, magne- to take their medications approval among prescribing healthcare providers and Both dolutegravir and sium, or buffered medicines, correctly, consistently, and PLWH. This may be due to reluctance to change viral- rilpivirine are generally Juluca should be taken (with achieve undetectable viral ly suppressive ART with a multi-tablet regimen or well tolerated. Side effects a meal, as always) at least loads can take advantage uncertainty with a two-drug regimen. observed in greater than 2% 4 hours before or 6 hours of this drug-sparing strategy. of study participants were after you take these medi- Currently people taking HIV ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: diarrhea and headache. cines. Alternatively, these treatment must start out 0 Juluca was approved for patients who have Dolutegravir and rilpivirine medications can be taken at with a three-drug regimen been virally suppressed for at least six months and can each cause a small, the same time with Juluca (which may include the use never experienced drug resistance to either of its reversible increase in a and the meal. Take Juluca of one of the single-tablet component medications. If you are concerned about kidney function test (serum with a meal 4 hours before regimens, or STRs), then the exposure to HIV medicines and their side effects creatinine) within the first or 12 hours after you take switch to Juluca after being but want to make sure your viral load continues to be few weeks of treatment H-2 blocker acid reducers undetectable for six months. suppressed, Juluca might be your option. Keep an eye without affecting actual (Pepcid, Zantac, Tagamet) Juluca still works against on your liver functions while taking Juluca. kidney function. There have or buffered medications. two steps of the life cycle of been rare reports of depres- Juluca should not be taken the virus, similar to 3-drug sion and suicidal ideation, with proton pump inhibitors regimens. This is how the Healthcare) is available in regimens containing dolute- primarily in patients with (such as Aciphex, Dexilant, combination was used in the STR Triumeq. Rilpivirine gravir are not recommended a history of psychiatric ill- Prilosec, Prevacid, Protonix, clinical studies to date. This (available separately under for use in ART-naïve nesses, in people receiving Nexium). Avoid taking combination was listed in the brand name Edurant, patients who are pregnant INSTI-based regimens. The Juluca with some seizure U.S. HIV guidelines as a from Janssen Therapeutics) and within 12 weeks of con- DHHS guidelines recom- medicines (carbamazepine, “Strategy with good support- is available in the STRs ception. Consult with your mend closely monitoring oxcarbazepine, phenobar- ing evidence” around the Complera and Odefsey. The provider to discuss guidance patients with pre-existing bital, and phenytoin) or time of its FDA approval. benefits of using Juluca, a on how to manage regimens psychiatric conditions on St. John’s wort. HIV treat- The guidelines also called two-drug regimen for HIV- containing dolutegravir or a an INSTI. Liver enzymes ment guidelines suggest Juluca “a reasonable option 1, include less exposure different integrase inhibitor should be monitored in that metformin be started when using nucleoside to HIV medications while if there is any possibility of people with hepatitis B or C at the lowest dose and drugs is not desirable” (for maintaining viral suppres- conception. and taking dolutegravir. Call titrated based on glycemic example, due to previous sion. Juluca is the smallest your health care provider control. Monitor for metfor- toxicity), with an A1 rat- STR, which may be advan- n MANUFACTURER right away if you develop min adverse effects. When ing (strong recommenda- tageous to individuals who ViiV Healthcare any of the following signs or starting or stopping Juluca tion based on randomized have difficulty swallowing. viivhealthcare.com symptoms: yellowing of the in people on metformin, controlled trials). Juluca New preliminary data from (877) 844-8872 skin or whites of the eyes; dose adjustment of metfor- is the first nucleoside-free an observational study in dark or tea-colored urine; min may be necessary to STR. Currently, all the STRs Botswana suggest that there n AVERAGE WHOLESALE PRICE pale-colored bowel move- maintain optimal glycemic contain two nucleoside may be an increased risk of $3,249.54/month ments; nausea or vomiting; control. Not intended to be drugs. Juluca contains two birth defects in infants born loss of appetite; or pain, taken with other HIV medi- currently available medica- to those who were receiv- aching, or tenderness on cations, unless prescribed tions. Dolutegravir (available ing dolutegravir at the time the right side below the ribs. that way. Tell your provider separately under the brand of conception. Until more There may be a possibility or pharmacist about all name Tivicay, from ViiV information is available,

30 MARCH+APRIL 2019 POSITIVELY AWARE positivelyaware.com/juluca 2019 POSITIVELY AWARE HIV DRUG GUIDE

darunavir/cobicistat/emtricitabine/ Symtuza tenofovir alafenamide (DRV/COBI/FTC/TAF) SINGLE-TABLET REGIMEN CONTAINING STR A PROTEASE INHIBITOR, A PHARMACOKINETIC RECOMMENDED INITIAL REGIMEN ENHANCER (BOOSTER), AND TWO NRTIs ✔ IN CERTAIN CLINICAL SITUATIONS n STANDARD DOSE • not recommended. Do not DR. DAVID HARDY SAYS: What makes Symtuza One tablet once daily with food for treatment-naïve take with betamethasone, unique among STRs is that it is the first one to people or people with suppressed viral load on a stable budesonide, carbamazepine, contain a boosted protease inhibitor. It will essentially HIV regimen for at least 6 months who have no known dexamethasone, dronedar- combine two currently available medications, resistance to the darunavir or tenofovir components of one, eslicarbazepine, ergot Prezcobix and Descovy, into one tablet which promis- the regimen. Tablet contains 800 mg darunavir, 150 mg derivatives, fluticasone, es to be smaller (more pharmaceutical magic) than cobicistat, 200 mg emtricitabine, and 10 mg tenofovir triazolam, oral midazolam, the size of a Prezcobix tablet (which is the largest STR alafenamide. lurasidone, methylpred- tablet to date). For PLWH who are doing well with a nisolone, oxcarbazepine, boosted protease inhibitor-containing regimen, Take missed dose as soon as possible, unless it is phenobarbital, phenytoin, Symtuza offers these folks the opportunity to experi- closer to the time of your next dose. Do not double up on pimozide, Revatio, simvas- ence the benefits of a one-tablet, once-a-day regimen your next dose. Dose cannot be adjusted for people with tatin, lovastatin, St. John’s for the first time. It is thought that many HIV-treating kidney or liver problems. Symtuza can be used in people wort, alfuzosin, ranolazine, healthcare providers now offer this new STR to their with an estimated creatinine clearance of at least 30 mL/ or rifampin. Not recom- patients on protease inhibitor-containing regimens. min. It should not be used in people with severe kidney mended to be taken with For those PLWH whose access or adherence to their or liver impairment. apixaban, avanafil, dabi- ART regimens is, or is predicted to be, difficult or gatran etexilate (in renal unreliable, this new STR offers them an option for a impairment), everolimus, proven “HIV resistance-resistant” ART regimen in one ➤ SEE THE INDIVIDUAL more information). Patients rifampentine, salmeterol, pill. On the other hand, many HIV-treating healthcare DRUGS CONTAINED IN experiencing a confirmed ticagrelor, or voriconazole. providers and PLWH are feeling increasingly confi- SYMTUZA: Prezista, increase in serum creatinine Beclomethasone and pred- dent that an integrase inhibitor-containing regimen Tybost, and Emtriva of greater than 0.4 mg/dL nisone as alternative cortico- (e.g., Triumeq, Biktarvy) is just as resistant-to-resis- (TAF is not marketed separately for HIV, but from baseline should be steriods may be considered, tance as a boosted protease inhibitor regimen and see also Descovy). closely monitored for renal particularly for long-term has better tolerability. Clinical trial data with Symtuza safety. Serum phosphorus use. Atorvastatin and rosu- and clinical experience with Prezcobix and Descovy ➤ SEE PACKAGE INSERT for in patients with or at risk for vastatin dose should not show that PLWH tolerate this regimen fairly well, but more complete informa- kidney impairment should exceed 20 mg daily. Clinical not as well as they tolerate unboosted integrase tion on potential side also be monitored. Prior to monitoring is recommended inhibitors (Triumeq, Biktarvy, and Isentress). Nausea, effects and interactions. initiation, people should with drospirenone, due to queasiness, diarrhea, and rash are most common be tested for hepatitis B potential for hyperkalemia. side effects seen with Symtuza or its components. n POTENTIAL SIDE EFFECTS (HBV) infection. Severe Do not take with colchicine AND TOXICITY exacerbations of hepatitis if there is kidney or liver ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: As darunavir contains a B have been reported in impairment. Can be used 0 This is the first once-a-day single-tablet regimen sulfa component, use with people who are co-infected with Daklinza. Cannot be containing a protease inhibitor, darunavir. One good caution in patients with with hepatitis B and have taken with Zepatier. Based thing about darunavir is that it has a high barrier to sulfa allergies. Side effects discontinued the emtric- on the mechanism, drug resistance. This also makes it a good candidate for most commonly reported itabine and/or tenofovir interactions with other treatment-naïve individuals as initial therapy. Because in studied subjects include components. Monitor liver hepatitis C medications of the way darunavir and cobicistat, a booster diarrhea (9%), rash (8%), enzymes closely in people are probably similar to the contained in Symtuza, are metabolized by the liver you nausea (6%), fatigue (4%), co-infected with hepatitis B interactions with Prezista will have to monitor for many drug-drug interactions headache (3%), abdominal and, if appropriate, initiation + Norvir + Descovy. Not that can cause serious problems. Among them, you will discomfort (2%), and flatu- of anti-hepatitis B therapy intended to be taken with find commonly prescribed drugs such as statins and lence (2%). While very rare, may be warranted. Although other HIV medications, some benzodiazepines (Halcion, for example). severe rash, accompanied some older PIs have been unless prescribed that way. in some cases by fever associated with liver toxic- Tell your provider or pharma- and/or elevations of AST/ ity, lactic acidosis, diabetes, cist about all medications, and there is never advisable Prezcobix (with cobicistat). ALT (liver enzymes), can or fat redistribution, these herbals, and supplements but does happen. As such, Compared with tenofovir DF, be life-threatening. Seek conditions are only rarely, or you are taking or thinking of a PI-based regimen such as the tenofovir alafenamide in medical attention immedi- never, seen with darunavir. taking, prescribed or not, as Symtuza suits some people Symtuza is safer on kidney ately. Observational cohort IRIS (immune reconstitution there are other drug interac- who may have trouble and bone health. Also as a studies reported an asso- inflammatory syndrome) tions which are not listed with the near-perfect drug result of the TAF, Symtuza ciation between some PIs may occur as the immune here. adherence required of HIV can be taken by people with (including darunavir when system regains strength; treatment. In fact, the FDA more advanced kidney dis- given with Norvir) and an signs and symptoms from n MORE INFORMATION allowed Janssen to adver- ease, down to a renal func- increased risk of cardiovas- previous infections may This medication was tise Symtuza as “help[s] tion (CrCL) of 30 mL/min. cular (CV) events, but data occur soon after HIV treat- approved last year and is protect against resistance.” with darunavir/cobicistat is ment is initiated. Report the first STR containing Symtuza may be used in n MANUFACTURER too limited to see such a symptoms of illness, such a protease inhibitor. This rapid initiation, treatment Janssen Therapeutics connection. With PIs, there as shingles or TB, to a formulation is much more given within 7 days of HIV Janssen Therapeutics can be increased bleeding health care provider. convenient and is associ- diagnosis, before resistance (800) JANSSEN in hemophiliacs. Cobicistat ated with fewer copays. A test results are available. (526-7736) can cause a small, revers- n POTENTIAL DRUG INTERACTIONS benefit of the PIs is their Treatment-experienced symtuza.com ible increase in serum cre- Do not take with Epivir- high genetic barrier to individuals with undetect- atinine (SCr, which indicates HBV, Hepsera, or Vemlidy the development of drug able viral loads for at least n AVERAGE WHOLESALE PRICE the eGFR or estimated CrCl (TAF), all three used for resistance. While medical six months may switch to $4,466.71/month lab values) within the first the treatment of hepatitis providers may hate to say it Symtuza. Darunavir is avail- few weeks of treatment B. Use with other prote- out loud, this means greater able under the brand name without affecting actual kid- ase inhibitors or Intelence, forgiveness of missed Prezista and is also found ney function (see Tybost for Sustiva, or Viramune is doses; missing a dose here in the co-formulated pill positivelyaware.com/symtuza POSITIVELY AWARE MARCH+APRIL 2019 31 2019 POSITIVELY AWARE HIV DRUG GUIDE

Delstrigo doravirine/lamivudine/tenofovir DF (DOR/3TC/TDF) STR SINGLE-TABLET REGIMEN CONTAINING RECOMMENDED INITIAL REGIMEN AN NNRTI AND TWO NRTIs ✔ IN CERTAIN CLINICAL SITUATIONS n STANDARD DOSE • n POTENTIAL DRUG INTERACTIONS DR. DAVID HARDY SAYS: Delstrigo was One tablet once daily without regard to food. Tablet New interactions continue approved in August 2018 and is the twelfth STR contains 100 mg of the NNRTI doravirine plus 300 mg to be discovered after drug and first “quasi-generic” STR approved by the FDA. lamivudine and 300 mg tenofovir DF (TDF). Approved approval (doravirine is the The term “quasi-generic” means that two of the com- only for adults at this time. new drug). Do not take ponents of Delstrigo, tenofovir DF and lamivudine, with Epivir-HBV, Hepsera, are from a generic, non-branded manufacturer, and Take missed dose as soon as possible, unless it is or Vemlidy (TAF), all three the Pifeltro (doravirine) is the branded drug made by closer to the time of your next dose. Do not double up on used for hepatitis B. When the manufacturer, Merck. Doravirine is considered to your next dose. Dose cannot be adjusted for people with using with the antibiotic be a “second generation” NNRTI due to its enhanced kidney problems; Delstrigo is not recommended in people drug rifabutin (used for resistance profile compared to Sustiva and Viramune with estimated creatinine clearance less than 50 mL/min. TB and to prevent MAC in and similar to other NNRTIs such as Intelence and Should not be used in people with moderate or severe AIDS patients), increase the Edurant. In fact, lab studies predict that it may be kidney impairment or severe liver impairment. doravirine dose by adding effective after a first generation NNRTI has failed and a Pifeltro tablet approxi- caused HIV resistance mutations or in PLWH with mately 12 hours later. The transmitted NNRTI resistance. To test this laboratory ➤ SEE THE INDIVIDUAL the Atripla group. Altered following medications may finding, a clinical trial called the DRIVE BEYOND DRUGS CONTAINED IN sensorium (e.g., lethargy, lower the blood levels of study, which enrolled ART treatment-naïve PLWH DELSTRIGO: Pifeltro, drowsiness, etc.) was asso- doravirine, and therefore with transmitted HIV resistance (K103N, Y181C, or Viread, and Epivir. ciated with 4% of people in may decrease its effective- G190A mutations), completed its initial follow-up in ➤ SEE PACKAGE INSERT for the Delstrigo group com- ness, and should not be late 2018. We look forward to hearing the outcome of more complete informa- pared to 8% of people in the used with Delstrigo: the this study in 2019. Data from two large clinical trials tion on potential side Atripla group. The doravirine anticonvulsants carbamaze- of treatment-naïve PLWH comparing Delstrigo to effects and interactions. component of Delstrigo did pine, oxcarbazepine, pheno- Sustiva (DRIVE AHEAD study) and to Prezista/Norvir not appear to negatively barbital, and phenytoin; the (DRIVE FORWARD study) have shown that Delstrigo n POTENTIAL SIDE EFFECTS affect cholesterol in studied androgen receptor inhibitor has similar anti-HIV potency as those two known AND TOXICITY populations. Decreases in enzalutamide; the antimy- potent medications with less treatment-limiting side The most common adverse bone mineral density (BMD) cobacterials rifampin and effects and less cholesterol-elevating effects. Of note reactions observed with have been observed in rifapentine; the cytotoxic and what will hopefully be a growing trend which Delstrigo in clinical trials patients on TDF-containing agent (cancer drug) mito- other newly approved STRs will follow, the 30-day (in more than at least 5% regimens. BMD monitoring tane; and the herbal St. wholesale acquisition cost (WAC) of Delstrigo is of people taking it) were should be considered in John’s wort. Avoid use of $2,100, compared to $2,950 for Biktarvy, $3,500 for dizziness (7%), nausea people who have a history sorbitol-containing medi- Symtuza, $2,800 for Triumeq, $3,000 for Genvoya and (5%), abnormal dreams of bone fracture due to bone cines with lamivudine; there Stribild, and $1,630 for Symfi and Symfi Lo. (5%), and increased lipase disease or are at risk for are many, such as acet- (5%). In one study (DRIVE- osteopenia or osteoporosis. aminophen liquid (Tylenol ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: AHEAD), an in-depth TDF may cause kidney tox- liquid and others). Epclusa 0 Delstrigo was approved for patients who have analysis was conducted icities. Creatinine clearance and Harvoni each increase not been treated with antiretrovirals before. In general, of the incidence of neuro- (CrCl) should be assessed the concentration of TDF; it is safe and well tolerated. If you have hepatitis B psychiatric adverse events before initiating treatment. monitor for adverse reac- (HBV) and are taking Delstrigo, do not stop taking it associated with Delstrigo In addition to CrCl, glucose tions. Not intended to be and make sure you never run out of it. This is not only compared to Atripla. and protein in the urine and taken with other HIV medi- because you want to maintain HIV viral suppression, Neuropsychiatric events, serum phosphorus should cations, unless prescribed which is a good reason, but, if you stop the medicine, such as depression, sleep be monitored more often that way. Tell your provider the HBV infection suddenly returns in a worse way disturbances, dizziness, in patients at risk for kidney or pharmacist about all than before. If for some reason you need to stop taking etc., are another common problems. Tell your provider medications, herbals, and Delstrigo, your doctor will need to monitor your HBV side effect of the NNRTI about any pain in extremi- supplements you are tak- infection by doing regular blood tests for a few months. class. The proportion of ties, persistent or worsening ing or thinking of taking, subjects who reported one bone pain and fractures, prescribed or not, as there or more neuropsychiatric with or without muscular are other drug interactions regimens in clinical trials were counted as virologic adverse events overall was pain or weakness, as well which are not listed here. yet. There is no data on the failures. See more data 24% for the Delstrigo group as any concerning changes safety of Delstrigo use in online. Merck has applied compared to 57% for the in urinary habits, as these n MORE INFORMATION pregnancy. to the FDA for a switch indi- Atripla group. The neuro- could be signs of kidney Stand-alone versions In the DRIVE-FORWARD cation, so that people with psychiatric adverse events problems. If you have HIV of doravirine (Pifeltro) study comparing doravirine undetectable viral load on associated with depres- and HBV, guidelines recom- and lamivudine/tenofovir to darunavir, results for the their current treatment can sion and suicide/self-injury mend treatment for both DF (Cimduo) were also treatment-naïve individu- switch to Delstrigo. were reported in 4% of the viruses. Delstrigo can be approved; see those pages. als in the study were 80% Delstrigo group compared used to treat HIV and HBV Unfortunately, Delstrigo (darunavir group) and 84% n MANUFACTURER to 7% of the Atripla group. simultaneously. If you are contains an older version (doravirine group) unde- Merck and Co. Overall, sleep disturbances co-infected with HBV and of tenofovir, TDF. A safer tectable (less than 50 viral (800) 622-4477 (e.g., abnormal dreams, HIV, you should not stop version, TAF, is available load). That’s a lower suc- delstrigo.com insomnia, nightmares, etc.) Delstrigo without medical and used in some STRs. cess rate than is expected were associated with 12% supervision because it can TDF is still an effective in HIV treatment today, but n AVERAGE WHOLESALE PRICE of people in the Delstrigo cause your HBV to flare and and quite tolerable medi- was thought to be affected $2,520.00/month group compared to 26% of cause you to experience cation, but TAF has less by the number of people people in the Atripla group. signs and symptoms of toxicity to the kidneys and who quickly dropped out Dizziness was associated acute hepatitis. HBV should bones. Doravirine has not of the study when they saw with 9% in the Delstrigo be closely monitored by been directly compared to how many pills they had group compared to 37% of your provider. integrase inhibitor-based to take. Those drop-outs

32 MARCH+APRIL 2019 POSITIVELY AWARE positivelyaware.com/delstrigo 2019 POSITIVELY AWARE HIV DRUG GUIDE

7 Dovato dolutegravir/lamivudine (DTG/3TC) SINGLE-TABLET REGIMEN INITIAL REGIMEN TO CONSIDER WHEN ABC, TAF, STR CONTAINING AN INSTI AND AN NRTI ✔ AND TDF CANNOT BE USED OR ARE NOT OPTIMAL n STANDARD DOSE • used in ART-naïve adults DR. DAVID HARDY SAYS: This combination is One tablet once daily, without regard to food. Tablet with baseline viral load less based upon the results of the GEMINI 1 and 2 contains 50 mg of the INSTI dolutegravir plus 300 mg than 500,000 in instances studies, in which treatment-naïve PLWH were of the NRTI lamivudine. where ABC, TDF, and TAF assigned to receive either the 2-drug combination cannot be used or are not regimen of Tivicay plus Epivir or the 3-drug Take missed dose as soon as possible, unless it is clos- optimal. (Other consider- combination of Tivicay and Truvada, which showed er to the time of your next dose. Do not double up on your ations for switching meds undetectable viral loads in 91% vs. 93% of study next dose. Lamivudine dosing needs to be adjusted for when one has undetectable participants, respectively, after one year of treatment. adults and children who have decreased kidney function viral load are also given.) Adverse events were uncommon and similar between (creatinine clearance less than 50 mL/min). See package The benefits of using a two- the two regimens, although there was more blood insert when available for guidance on dosing in the setting drug regimen for HIV include biochemical evidence of bone and kidney damage of kidney impairment. Dolutegravir is not recommended less exposure to HIV medi- with the 3-drug (tenofovir DF-containing) regimen for people with severe liver impairment. cation while maintaining compared to the 2-drug regimen. Of note, virologic viral suppression and also failure was seen in 4 and 2 study participants, minimizing the potential for respectively, with no evidence of any virologic ➤ SEE THE INDIVIDUAL and cause you to experi- side effects. See data online. resistance with either regimen. These two clinical DRUGS CONTAINED IN ence signs and symptoms New preliminary data from trials are the first to show that a 2-drug, non-boosted THIS MEDICATION: Tivicay of acute hepatitis. HBV an observational study in regimen works as well as a 3-drug regimen. How HIV- and Epivir. should be closely moni- Botswana suggest that there treating medical care providers and PLWH will accept ➤ SEE PACKAGE INSERT for tored by your provider. may be an increased risk of this paradigm-changing, 2-drug regimen as first-line more complete informa- birth defects in infants born therapy is yet to be seen. Of note, both the DHHS and tion on potential side n POTENTIAL DRUG INTERACTIONS to those who were receiv- IAS-USA guidelines include this regimen only as an effects and interactions. Do not take Dovato with ing dolutegravir at the time alternative regimen when Truvada, TAF, or Epzicom Epivir-HBV. When taking of conception. Until more cannot be tolerated. The TANGO study is randomizing n POTENTIAL SIDE EFFECTS carbamazepine or rifampin, information is available, reg- 550 treatment-experienced PLWH with undetectable AND TOXICITY take an additional dose of imens containing dolutegra- viral loads and no history of viral resistance to switch Dolutegravir and lami- dolutegravir (in the form of vir are not recommended for to Tivicay/Epivir (in a fixed-dose-combination tablet) vudine are both generally one Tivicay tablet) 12 hours use in ART-naïve patients or remain on their current ART regimen. TANGO well tolerated. The most after taking your Dovato who are pregnant and with- began enrollment in February 2018 and is expected to common adverse events dose. When starting or stop- in 12 weeks of conception. produce results in 2020. (in 5% or more of people ping dolutegravir in people Additionally, regimens con- taking it) in the GEMINI-1 on metformin, dose adjust- taining dolutegravir should ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: and GEMINI-2 studies ment of metformin may be not be used in people of 0 When you are HIV positive, if you are in treat- combined were headache necessary to maintain opti- childbearing potential who ment, and virally suppressed, your life expectancy (10%), diarrhea (9%), and mal glycemic control. Avoid are sexually active and not increases. Lifetime drug adherence is needed to fully nasopharyngitis (allergy- use of sorbitol-containing using effective contracep- get the benefits of the HIV drug regimen taken. By the like symptoms, 8%). medicines with lamivu- tion or who are planning same token, one is exposed to potential long-term Dolutegravir can cause a dine; there are many, such to become pregnant. It is adverse effects. Some are known and others, those small, reversible increase in as acetaminophen liquid unclear whether dolutegravir that might show after longtime exposure, are still not kidney function test (serum (Tylenol liquid and others). is the only integrase inhibitor known completely. Dual-drug HIV treatment regimens creatinine) within the first Should be okay to take with with the potential to cause can potentially lessen drug exposure, not only for few weeks of treatment Daklinza, Epclusa, Harvoni, these birth defects (neural those on treatment but also for those considering without affecting actual Olysio, Sovaldi, Viekira Pak, tube defects), or if other treatment for the first time. Development of drug kidney function. There have or Zepatier. Not intended integrase inhibitors also cross-resistance is something to take into consider- been rare reports of depres- to be taken with other carry this risk. Consult your ation when you start treatment for the first time. The sion and suicidal ideation, HIV medications, unless provider to discuss guidance challenge is to find powerful drugs with a high genetic primarily in patients with prescribed that way. Tell on how to manage regimens barrier to drug resistance. Recent research (GEMINI 1 a history of psychiatric ill- your provider or pharma- containing dolutegravir or a and 2 studies) has proven that dual treatment with nesses, in people receiving cist about all medications, different integrase inhibitor the two-drug combination of dolutegravir (DTG) plus INSTI-based regimens. The herbals, and supplements if there is any possibility of lamivudine (3TC) is not inferior to triple ART combina- DHHS guidelines recom- you are taking or thinking of conception. tion. GEMINI 1 and 2 are identically designed studies. mend closely monitoring taking, prescribed or not, as Both are large Phase 3 studies in which 700 treat- patients with pre-existing there are other drug interac- n MANUFACTURER ment-naïve individuals were randomized to either psychiatric conditions on tions which are not listed ViiV Healthcare DTG+3TC or DTG+TDF/FTC. The primary endpoint an INSTI. Liver enzymes here. viivhealthcare.com was reaching plasma viral load less than 50 copies at should be monitored in (877) 844-8872 week 48. This treatment strategy looks promising. people with hepatitis B or n MORE INFORMATION More research needs to be done. C and taking dolutegravir. Basically, this medicine is n AVERAGE WHOLESALE PRICE 3TC can treat both HIV and Triumeq without the aba- $2,754.00/month HBV, but must be used in cavir (brand name Ziagen, combination with another also found in Epzicom). hep B drug (such as teno- Dolutegravir is from the fovir) to treat the hep B. If powerhouse drug class of you are co-infected with integrase inhibitors, which HBV and HIV, you should are highly effective and not stop 3TC without medi- generally tolerable. This cal supervision because it coformulated STR is recom- can cause your HBV to flare mended by guidelines to be positivelyaware.com/dovato POSITIVELY AWARE M A R CH + A P RIL 201 9 33 2019 POSITIVELY AWARE HIV DRUG GUIDE

elvitegravir/cobicistat/emtricitabine/ Genvoya tenofovir alafenamide (EVG/COBI/FTC/TAF) STR SINGLE-TABLET REGIMEN CONTAINING RECOMMENDED INITIAL REGIMEN A BOOSTED INSTI AND TWO NRTIs ✔ IN CERTAIN CLINICAL SITUATIONS n STANDARD DOSE • to systemic dexametha- DR. DAVID HARDY SAYS: Genvoya, the fifth STR One tablet once daily with food. Tablet contains 150 mg sone should be considered. approved, in 2015, is commonly called the “new of the INSTI elvitegravir boosted by 150 mg cobicistat Risks versus benefits of and improved” version of Stribild because it contains plus 200 mg emtricitabine and 10 mg tenofovir alafen- using with voriconazole three of the four medications that Stribild contains. amide (TAF). should be assessed with What makes Genvoya different is that the Viread expert consultation. Some component of Stribild has been “updated” with a new For adults and children weighing at least 55 pounds cholesterol-lowering drugs medication called TAF (tenofovir alafenamide fuma- (25 kg) and having a creatinine clearance of at least such as atorvastatin should rate). TAF is known as a “prodrug,” which means that 30 mL/min (measurement of kidney function), as well as be used with caution and it’s kind of like a “prequel”—it comes before the older, adults with creatinine clearance below 15 mL/min who started at the lowest dose already known version and is changed into the active are receiving chronic hemodialysis (HD). For those on HD, possible. Monitor closely drug (tenofovir) within the body. TAF is kind of like take tablet after completion of hemodialysis on days of for increased side effects tenofovir DF, but through pharmaceutical magic, the HD treatment. from these medications, amount of tenofovir needed to effectively suppress Take missed dose as soon as possible, unless it is such as muscle pain. HIV has been reduced from 300 mg in Stribild to only closer to the time of your next dose. Do not double up on Concentrations of antide- 10 mg in Genvoya. This 97% reduction means that your next dose. Dose cannot be adjusted for people with pressants such as fluox- there is much less tenofovir in the blood of PLWH tak- liver problems. Genvoya is not recommended for people etine, paroxetine, bupropion, ing Genvoya and therefore much less chance of kid- who have severe liver problems, a CrCl between 15 to or amitriptyline may be ney- or bone mineral density- (solidness of bone) 30 mL/min, or a CrCl less than 15 mL/min who are not increased, and their doses harming side effects. Clinical trials have shown that receiving chronic hemodialysis. may need to be reduced. Genvoya is similar to (just as good as) Stribild for Genvoya increases levels of treating HIV, and it has significantly fewer negative many nasal and inhaled ste- side effects on both kidneys and bones. Further, addi- ➤ SEE THE INDIVIDUAL Severe exacerbations of roids like fluticasone, which tional small studies proved that Genvoya can be safe- DRUGS CONTAINED IN hepatitis B have been may lead to symptoms of ly used in PLWH with pre-existing mild to moderate GENVOYA: Emtriva and reported in people who are Cushing’s syndrome. An kidney disease. Like Stribild, however, Genvoya con- Tybost (elvitegravir is not co-infected with hepatitis B alternative corticosteroid tains a “booster” (cobicistat or Tybost) which is asso- available separately, and neither is TAF for use in and have discontinued the to fluticasone is recom- ciated with interactions with other medications which HIV, but see Descovy). emtricitabine and/or teno- mended. Cialis, Levitra, and PLWH may take. Of note, the most recent versions of fovir components. Monitor Viagra levels are increased; both the DHHS and IAS-USA guidelines have ➤ SEE PACKAGE INSERT for liver enzymes closely in doses should not exceed removed both Stribild and Genvoya from their first more complete informa- people co-infected with hep- 10 mg Cialis or 2.5 mg line of “recommended for all PLWH” categories and tion on potential side atitis B and, if appropriate, Levitra per 72 hours, or 25 placed them in a category for special situations. effects and interactions. initiation of anti-hepatitis B mg Viagra per 48 hours. therapy may be warranted. Monitor for increased side ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: n POTENTIAL SIDE EFFECTS effects of these medications. 0 Because cobicistat, a booster contained in AND TOXICITY n POTENTIAL DRUG INTERACTIONS Effectiveness of oral contra- Genvoya, is metabolized by the liver, you will have to Common side effects Do not take with Epivir-HBV, ceptives may be decreased; monitor for many drug-drug interactions that can reported in at least 5% of Hepsera, or Vemlidy consider using alternative cause serious problems. Among them you will find study participants include (TAF), all three used for or additional contraception commonly prescribed medications such as statins, nausea, diarrhea, headache, the treatment of hepatitis methods. Reduce Daklinza erectile dysfunction drugs, and some and fatigue. Before taking B. Separate by at least 2 dose to 30 mg. Can be benzodiazepines. Genvoya, kidney function hours from antacids con- taken with Harvoni. Taking testing should be conducted, taining aluminum, magne- with Olysio, Viekira Pak, including serum creatinine, sium hydroxide, or calcium or Zepatier is not recom- made due to the presence an observational study in serum phosphorus, urine carbonate. Safe to take mended. Monitor kidney of the booster cobicistat, Botswana suggest that there glucose, and urine pro- with other medications function more closely with which has many drug inter- may be an increased risk of tein. These measurements used for heartburn and Epclusa. Not intended to be actions, and because these birth defects in infants born should continue to be moni- GERD such as Nexium, taken with other HIV medi- meds do not have the high to those who were receiv- tored while taking Genvoya. Pepcid, Prevacid, Prilosec, cations, unless prescribed barrier to drug resistance ing dolutegravir at the time Cobicistat can cause a and Zantac. Cobicistat has that way. Tell YOUR provider that Biktarvy, Tivicay, and of conception. Consult your small, reversible increase in many drug interactions simi- or pharmacist about all Triumeq have. Last year, provider to discuss guidance serum creatinine within the lar to Norvir. Do not take medications, herbals, and Genvoya was approved for on how to manage regimens first few weeks of treatment with cholesterol-lowering supplements you are tak- use in patients on hemodi- containing an integrase without affecting actual drugs containing lovastatin ing or thinking of taking, alysis; however, doctors are inhibitor if there is any pos- kidney function (see Tybost or simvastatin (Advicor, prescribed or not, as there also using off-label prescrib- sibility of conception. for more information). There Altoprev, Mevacor, Simcor, are many other drug interac- ing of Biktarvy or Juluca for have been rare reports of Vytorin, Zocor), alfuzosin, tions not listed here. patients on hemodialysis. n MANUFACTURER depression and suicidal ide- carbamazepine, phenobar- Genvoya is not recommend- Gilead Sciences, Inc. ation, primarily in patients bital, phenytoin, ergotamine, n MORE INFORMATION ed for use in pregnancy gilead.com; genvoya.com with a history of psychiatric dihydroergotamine, methy- For a while very popular, due to substantially lower (800) GILEAD-5 illnesses, in people receiv- lergonovine, oral midazol- Genvoya, along with its exposures of cobicistat (445-3235) ing INSTI-based regimens. am, lurasidone, pimozide, sister med Stribild, were and elvitegravir during the The DHHS guidelines rec- Revatio, rifampin, rifabutin, recently downgraded in U.S. second and third trimesters n AVERAGE WHOLESALE PRICE ommend closely monitoring rifapentine, Serevent, tri- HIV treatment guidelines, as well as reports of viral $3,534.78/month patients with pre-existing azolam, or St. John’s wort. from “recommended initial breakthrough. Switching psychiatric conditions on Dose of clarithromycin may therapy for most people” regimens should be consid- an INSTI. Prior to initiation, need to be reduced based to “recommended initial ered for pregnant women people should be tested for on kidney function. An therapy in certain clinical already taking this regimen. hepatitis B (HBV) infection. alternative corticosteroid situations.” The change was New preliminary data from

34 MARCH+APRIL 2019 POSITIVELY AWARE positivelyaware.com/genvoya 2019 POSITIVELY AWARE HIV DRUG GUIDE

Stribild elvitegravir/cobicistat/emtricitabine/tenofovir DF (EVG/COBI/FTC/TDF) STR SINGLE-TABLET REGIMEN CONTAINING RECOMMENDED INITIAL REGIMEN A BOOSTED INSTI AND TWO NRTIs ✔ IN CERTAIN CLINICAL SITUATIONS n STANDARD DOSE • used with caution and DR. DAVID HARDY SAYS: Stribild was the third One tablet once daily with food. Tablet contains started at the lowest dose STR to be approved, in 2012, and the first STR 150 mg of the INSTI elvitegravir boosted by possible. Monitor closely to contain an integrase inhibitor medication (elvitegra- 150 mg cobicistat plus 200 mg emtricitabine and for increased side effects vir, formerly Vitekta) as well as the first to contain the 300 mg tenofovir disoproxil fumarate (TDF). from these medications, “booster” Tybost (cobicistat). In order for the elvitegra- such as muscle pain. vir part of Stribild to be given once a day and effective- For adults and children 12 years of age and older Concentrations of antide- ly suppress HIV, it must be given with a “booster”, like weighing at least 77 pounds (35 kg). pressants such as fluox- Tybost (cobicistat) or Norvir. Studies of Stribild com- Take missed dose as soon as possible, unless it is etine, paroxetine, bupropion, paring it to either Atripla or Reyataz/Norvir-containing closer to the time of your next dose. Do not double up on or amitriptyline may be ART regimens in PLWH starting their first ART regi- your next dose. Dose cannot be adjusted for people with increased by Stribild, and men showed that it was similar to (just as good as) kidney or liver problems. Stribild should not be started in their doses may need to be these two regimens. Due to these favorable compari- individuals with estimated CrCl less than 70 mL/min and reduced. Use with caution sons, Stribild was recommended as a first-line ART should be discontinued if CrCl decreases to less than 50 and therapeutic monitor- regimen since it was first approved, but in 2018 it fell mL/min. Stribild is not recommended for patients with ing, if available, for antiar- out of both the DHHS and IAS-USA guidelines as a severe liver problems, or during pregnancy. rhythmic drugs like digoxin. recommended first-line ART regimen for all PLWH due Stribild increases levels of to its booster (side effects and drug-drug interactions) many nasal and inhaled ste- and history of lower genetic barrier to viral resistance. ➤ SEE THE INDIVIDUAL co-infected with hepatitis B roids like fluticasone, which Because Stribild contains Viread, PLWH who have pre- DRUGS CONTAINED and have discontinued the may lead to symptoms of existing mild to moderate kidney disease, or who IN STRIBILD: Emtriva, emtricitabine and/or teno- Cushing’s syndrome. An develop moderate kidney disease, should not receive Viread, and Tybost fovir components. Monitor alternative corticosteroid to Stribild. This limitation of Stribild has been improved (elvitegravir is not avail- liver enzymes closely in fluticasone is recommend- with the availability of newer STRs. The use of Stribild able separately). people co-infected with ed. Use caution with beta was previously strong, but due to availability of newer ➤ SEE PACKAGE INSERT for hepatitis B and, if appro- blockers and calcium chan- STRs with less side effects and fewer drug interac- more complete informa- priate, initiation of anti- nel blockers. Cialis, Levitra, tions, its use continues to decrease. tion on potential side hepatitis B therapy may be and Viagra levels are effects and interactions. warranted. increased; doses should not ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: exceed 10 mg Cialis or 2.5 0 It is important to monitor the kidneys and bone n POTENTIAL SIDE EFFECTS n POTENTIAL DRUG INTERACTIONS mg Levitra per 72 hours, or density while taking Stribild. If there are changes in AND TOXICITY Do not take with Epivir- 25 mg Viagra per 48 hours. your bone density or your kidney functions, ask your Common side effects HBV, Hepsera, or Vemlidy Monitor for increased side doctor to switch you to Genvoya or Biktarvy. Because reported in 10% or more of (TAF), all three used for effects of these medications, of cobicistat, Stribild has serious drug interactions study participants include the treatment of hepatitis such as visual disturbances. that either increase or decrease the levels of com- nausea and diarrhea. Other B. Separate by at least 2 Effectiveness of oral contra- monly prescribed drugs such as some statins, benzos, less common side effects hours from antacids con- ceptives may be decreased; and erectile dysfunction drugs. Remember to take it include abnormal dreams taining aluminum, magne- consider using alternative with food. and headache. Before tak- sium hydroxide, or calcium or additional contraception ing Stribild, kidney function carbonate. Stribild is safe methods. Co-administer testing should be conducted to take with other medica- bosentan and immuno- patients on hemodialysis. an observational study in including serum creatinine, tions used for heartburn suppressants like Prograf, Genvoya along with its Botswana suggest that serum phosphorus, urine and GERD, such as Nexium, Gengraf, Neoral, and sister med Stribild were there may be an increased glucose, and urine pro- Pepcid, Prevacid, Prilosec, Sandimmune with cau- recently downgraded in U.S. risk of birth defects in tein. These measurements and Zantac. Do not take tion. Reduce Daklinza dose HIV treatment guidelines, infants born to those who should continue to be moni- Stribild with alfuzosin, car- to 30 mg. Taking with from “recommended initial were receiving dolutegravir tored while taking Stribild. bamazepine, phenobarbital, Harvoni, Olysio, Viekira therapy for most people” at the time of conception. It Cobicistat can cause a phenytoin, ergotamine, Pak, or Zepatier is not rec- to “recommended initial is unclear whether dolute- small, reversible increase in dihydroergotamine, methy- ommended. Monitor kidney therapy in certain clinical gravir is the only integrase serum creatinine within the lergonovine, oral midazolam, function more closely with situations.” The change was inhibitor with the potential first few weeks of treatment pimozide, Revatio, rifampin, Epclusa. Not intended to be made due to the presence to cause these birth defects without affecting actual kid- rifabutin, rifapentine, taken with other HIV medi- of the booster cobicistat, (neural tube defects), or if ney function (see Tybost for Serevent, triazolam, or St. cations, unless prescribed which has many drug inter- other integrase inhibitors more information). There John’s wort. An alternative that way. Tell your provider actions, and because these also carry this risk. Consult have been rare reports of corticosteroid to systemic or pharmacist about all meds do not have the high your provider to discuss depression and suicidal ide- dexamethasone should be medications, herbals, and barrier to drug resistance guidance on how to manage ation, primarily in patients considered. No significant supplements you are tak- that Biktarvy, Tivicay, and regimens containing dolute- with a history of psychiatric interactions with beclo- ing or thinking of taking, Triumeq have. Stribild is gravir or a different inte- illnesses, in people receiv- methasone or prednisolone. prescribed or not, as there not recommended for use grase inhibitor if there is any ing INSTI-based regimens. Risks versus benefits of are many other drug interac- in pregnancy due to sub- possibility of conception. The DHHS guidelines rec- using Stribild and voricon- tions not listed here. stantially lower exposures ommend closely monitoring azole together should be of cobicistat and elvitegra- n MANUFACTURER patients with pre-existing assessed with expert con- n MORE INFORMATION vir during the second and Gilead Sciences, Inc. psychiatric conditions on sultation. Do not use with The newer version of third trimesters as well gilead.com an INSTI. Prior to initiation, lovastatin or simvastatin this drug, Genvoya, was as reports of viral break- stribild.com people should be tested for (Advicor, Altoprev, Mevacor, approved for use in patients through. Switching regimen (800) GILEAD-5 hepatitis B (HBV) infec- Simcor, Vytorin, and Zocor). on hemodialysis last year; or close monitoring should (445-3235) tion. Severe exacerbations Cholesterol-lowering drugs however, doctors are also be considered for those of hepatitis B have been such as rosuvastatin and using off-label prescribing already taking this regimen. n AVERAGE WHOLESALE PRICE reported in people who are atorvastatin should be of Biktarvy or Juluca for New preliminary data from $3,707.99/month positivelyaware.com/stribild POSITIVELY AWARE MARCH+APRIL 2019 35 2019 POSITIVELY AWARE HIV DRUG GUIDE

Odefsey rilpivirine/emtricitabine/tenofovir alafenamide (RPV/FTC/TAF) STR SINGLE-TABLET REGIMEN CONTAINING RECOMMENDED INITIAL REGIMEN AN NNRTI AND TWO NRTIs ✔ IN CERTAIN CLINICAL SITUATIONS n STANDARD DOSE • Use azithromycin when DR. DAVID HARDY SAYS: Odefsey is the sixth One tablet once daily, with a standard meal (more than possible instead of the STR approved, in 2016, and is commonly 390 calories). See below. Tablet contains 25 mg of the antibiotics clarithromycin, considered the “new and improved” version of NNRTI rilpivirine plus 200 mg emtricitabine and 25 mg erythromycin, or telithro- Complera. Clinical trials have shown that switching tenofovir alafenamide (TAF). mycin, because these PLWH who are receiving Atripla or Complera to drugs increase rilpivirine Odefsey results in similar (as good as) results in terms Must be taken with a meal that you chew—not just levels, which can increase of suppressing their HIV compared to keeping them nutritional drinks or protein shakes. Taking rilpivirine the risk for side effects. on their initial ART regimen. Those PLWH switched without food could result in a 40% decrease in drug Reduced methadone levels from Atripla to Odefsey also had decreased side absorption and may lead to resistance. can occur and while dose effects (grogginess, vivid dreams) compared to those People taking HIV treatment for the first time must adjustments are not nec- who continued Atripla. Odefsey continues to have the have an HIV RNA (viral load) of less than 100,000 cop- essary, it is recommended same potency problems that Complera has, that is, it ies/mL and a CD4 T-cell count of more than 200 cells/ to monitor for withdrawal is not as effective in suppressing initial high viral mm3 before starting Odefsey due to higher rates of viro- symptoms. Odefsey should loads in PLWH (>100,000 copies/ml). Similar to logic failure in these patients. also not be taken with other Complera, Odefsey is well tolerated by PLWH, with For adults and children 12 years of age and older medications that prolong minimal to rare side effects. Therefore, Odefsey has weighing at least 77 pounds (35 kg) and having a CrCl of QTc interval or medica- not been recommended for initial treatment for all at least 30 mL/min. tions with a known risk of PLWH, but rather only those with low initial viral Take missed dose as soon as possible, unless it is torsades de pointes. May loads (<100,000 copies/ml). Although not specifically closer to the time of your next dose. Do not double up on be taken with Daklinza, studied, Odefsey’s use as an ART switch regimen for your next dose. Harvoni, Olysio, Sovaldi, PLWH with undetectable viral loads off of a regimen Zepatier, or Epclusa. Cannot associated with side effects (e.g., protease inhibitor) be taken with Viekira Pak. would probably work well as it did with Complera. ➤ SEE THE INDIVIDUAL and have discontinued the Not intended to be taken DRUGS CONTAINED IN emtricitabine and/or teno- with other HIV medications, ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: ODEFSEY: Edurant and fovir components. Monitor unless prescribed that way. 0 Odefsey is a once-a-day single-tablet regimen Descovy (co-formulation liver enzymes closely in Tell your provider or pharma- that contains two HIV nucleoside analog reverse tran- of Emtriva and TAF). people co-infected with cist about all medications, scriptase inhibitors (emtricitabine, tenofovir alafen- ➤ SEE PACKAGE INSERT for hepatitis B and, if appro- herbals, and supplements amide) and a non-nucleoside reverse transcriptase more complete informa- priate, initiation of anti- you are taking or thinking inhibitor (rilpivirine). Odefsey is comparable to tion on potential side hepatitis B therapy may be of taking, prescribed or Complera; the difference is that Odefsey contains effects and interactions. warranted. not, as there are other drug tenofovir alafenamide instead of tenofovir disoproxil, interactions which are not reducing the risk for kidney toxicity and loss of bone n POTENTIAL SIDE EFFECTS n POTENTIAL DRUG INTERACTIONS listed here. density. This single-tablet regimen is recommended AND TOXICITY Do not take with Epivir- in certain clinical situations for individuals who have Moderate to severe side HBV, Hepsera, or Vemildy n MORE INFORMATION not yet been treated for HIV, and have a viral load less effects are uncommon; (TAF), all three used for Odefsey is a single-tablet than or equal to 100,000 copies. It is also prescribed insomnia, headache, and the treatment of hepatitis regimen that is an option to individuals with previous HIV antiretroviral treat- depressive disorders B. Proton pump inhibitors for people with impaired ment who are virally suppressed (less than 50 copies) (depression, negative (PPIs, heartburn or stom- kidney function. Rilpivirine- for at least six months, with no history of treatment thoughts, suicidal thoughts ach acid drugs like Aciphex, containing regimens can failure related to developing resistance to the other or actions) were each Dexilant, Nexium, Prevacid, be relatively difficult to medicines contained in Odefsey. Consult your doctor reported in 2% of study Prilosec, Protonix, etc.) take because of their food about all medications you are taking, prescribed or participants on rilpivirine- can’t be taken with Odefsey. requirement and drug inter- over-the-counter. Serious drug interactions can containing regimens. Cases Antacids containing alumi- actions. In addition, strict occur. If you feel extremely depressed or suffering of rash and increased liver num, magnesium hydroxide, adherence is critical due to insomnia, tell your doctor. Damage to the liver or kid- enzymes have also been or calcium carbonate can the relatively low barrier to neys is a possibility when taking Odefsey. Make sure reported with regimens be taken two hours before the development of resis- your doctor monitors liver and kidney functions. If you containing rilpivirine. There or four hours after Odefsey. tance. The Odefsey tablet experience an allergic reaction call your doctor imme- may be a small increase Stomach acid-reducing is very small in size, which diately and stop taking Odefsey. in serum creatinine (SCr) drugs like Pepcid, Tagamet, may be advantageous to and decrease in estimated and Zantac can be taken 12 individuals who have dif- creatinine clearance (CrCl) hours before or four hours ficulty swallowing. associated with rilpivirine. after a dose of Odefsey. See Descovy page for other Do not take with carba- n MANUFACTURER possible effects on kidney mazepine, oxcarbazepine, Gilead Sciences, Inc. function. The most com- phenobarbital, phenytoin, gilead.com mon (greater than 10%) rifampin, rifapentine, or the odefsey.com side effect seen in clinical herb St. John’s wort. Taking (800) GILEAD-5 trials with Descovy (the Odefsey with rifabutin is not (445-3235) fixed-dose combination recommended. Do not take of Emtriva and TAF) is with more than one dose of Janssen Therapeutics nausea. Prior to initiation, the injectable steroid dexa- janssentherapeutics.com people should be tested methasone (sometimes (800) JANSSEN for hepatitis B (HBV) infec- given in the ER or hospital). (526-7736) tion. Severe exacerbations Use caution if used with of hepatitis B have been fluconazole, itraconazole, n AVERAGE WHOLESALE PRICE reported in people who are ketoconazole, posacon- $3,216.92/month co-infected with hepatitis B azole, and voriconazole.

36 M A R CH + A P RIL 201 9 POSITIVELY AWARE positivelyaware.com/odefsey 2019 POSITIVELY AWARE HIV DRUG GUIDE

Complera rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) STR SINGLE-TABLET REGIMEN CONTAINING RECOMMENDED INITIAL REGIMEN AN NNRTI AND TWO NRTIs ✔ IN CERTAIN CLINICAL SITUATIONS n STANDARD DOSE • to Complera. Do not take DR. DAVID HARDY SAYS: Complera was the sec- One tablet once daily, with a standard meal (more than with more than one dose of ond STR approved in the U.S., in 2011. At that 390 calories) for adults and children 12 years of age the injectable steroid dexa- time, it was the first alternative STR to Atripla and and older weighing at least 77 pounds (35 kg). Tablet methasone (sometimes offered PLWH a single, once-a-day pill which could contains 25 mg of the NNRTI rilpivirine plus 200 mg given in the ER or hospital). (and was recommended) to be taken with food. It emtricitabine and 300 mg tenofovir DF (TDF). Use caution if used with does not have the pesky grogginess and vivid dreams fluconazole, itraconazole, associated with Atripla. While Complera’s side effects Must be taken with a meal that you chew—not just ketoconazole, posacon- are better than Atripla’s, its potency has always been nutritional drinks or protein shakes. Taking rilpivirine azole, and voriconazole. somewhat questionable in PLWH with high initial viral without food could result in a 40% decrease in drug Use azithromycin when loads (greater than 100,000 copies/mL). On the other absorption and may lead to resistance. possible instead of the hand, Complera’s side effects have been minimal and People taking HIV treatment for the first time must antibiotics clarithromycin, therefore well tolerated by PLWH. Primarily due to its have an HIV RNA (viral load) of less than 100,000 erythromycin, or telithro- lack of potency, it has never been recommended as a copies/mL and a CD4 T-cell count of more than 200 mycin, because these drugs starting regimen for all PLWH. Since the development cells/mm3 before starting Complera due to higher rates increase rilpivirine levels, of the “new and improved” version of Complera, of virologic failure in these patients. which can increase the risk called Odefsey, Complera’s use has decreased and, Take missed dose as soon as possible, unless it’s closer of side effects. Reduced because it has fallen further out of the recommended to the time of your next dose. Do not double up on your methadone levels can occur ART guidelines due to the issues above, it is rarely next dose. Complera should not be used in people with and while dose adjustments prescribed today. CrCl less than 50 mL/min or severe liver impairment. are not necessary, it is recommended to monitor ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: for withdrawal symptoms. 0 Complera is the combination of three HIV ➤ SEE THE INDIVIDUAL anti-hepatitis B therapy Complera should also not medicines contained in one single tablet and taken DRUGS CONTAINED IN may be warranted. be taken with other medi- once a day. It is comparable to Odefsey as it combines COMPLERA: Edurant and cations that prolong QTc rilpivirine with emtricitabine and the original tenofovir Truvada (co-formulation n POTENTIAL DRUG INTERACTIONS interval (a heart problem) disoproxil fumarate while Odefsey contains tenofovir of Emtriva and Viread). Tell your provider or or medications with a alafenamide. Complera is recommended as an initial ➤ SEE PACKAGE INSERT for pharmacist about all known risk of torsades de therapy in certain clinical situations for individuals more complete informa- medications, herbals, and pointes. Complera may with a viral load less than 100,000 copies. It could tion on potential side supplements you are tak- be taken with Daklinza, also be prescribed to those wanting to replace their effects and interactions. ing or thinking of taking, Harvoni, Olysio, Sovaldi, current regimen and have had suppressed viral load prescribed or not, as there and Zepatier. Monitor for (less than 50 copies) for at least six months. It is not n POTENTIAL SIDE EFFECTS are other drug interactions tenofovir toxicities with recommended if the reason for replacement is due to AND TOXICITY which are not listed here. Epclusa. Complera cannot developing resistance to other antivirals, more so Moderate to severe Do not take with Epivir-HBV, be taken with Viekira Pak. those contained in Complera. You need to watch for side effects are uncom- Hepsera, or Vemlidy (TAF), Not intended to be taken drug-drug interactions and changes in liver and mon. Insomnia, headache, all three used for treatment with other HIV medica- kidney functions. and depressive disorders of hepatitis B. Proton pump tions, unless prescribed (depression, negative inhibitors (PPIs, heartburn that way. Tell YOUR pro- thoughts, suicidal thoughts or stomach acid drugs like vider or pharmacist about n MANUFACTURER or actions) were each Aciphex, Dexilant, Nexium, all medications, herb- Gilead Sciences, Inc. reported in 2% of study Prevacid, Prilosec, Protonix, als, and supplements gilead.com participants. Cases of etc.) can’t be taken with you are taking or thinking complera.com rash and increased liver Complera. Antacids con- of taking, prescribed or (800) GILEAD-5 enzymes have also been taining aluminum, magne- not, as there are other drug (445-3235) reported with regimens sium hydroxide, or calcium interactions which are not containing rilpivirine. There carbonate can be taken at listed here. Janssen Therapeutics may be a small increase least two hours before or janssentherapeutics.com in serum creatinine (SCr) at least four hours after a n MORE INFORMATION (800) JANSSEN and decrease in estimated Complera dose. Stomach Complera can be relatively (526-7736) creatinine clearance (CrCl) acid-reducing drugs like difficult to take because of associated with rilpivirine. Pepcid, Tagamet, and its food requirement and n AVERAGE WHOLESALE PRICE See Truvada page for other Zantac can be taken at least drug interactions. In addi- $3,216.92/month possible effects on kidney 12 hours before or at least tion, strict adherence is function. Prior to initiation, four hours after a Complera critical due to its relatively people should be tested dose. Do not take Complera low barrier to the devel- for hepatitis B (HBV) infec- with carbamazepine, oxcar- opment of resistance. A tion. Severe exacerbations bazepine, phenobarbital, newer version of Complera, of hepatitis B have been phenytoin, rifampin, rifa- Odefsey, contains tenofovir reported in people who are pentine, or the herb St. alafenamide (TAF) instead co-infected with hepatitis John’s wort (other herbals of tenofovir DF; TAF is safer B and have discontinued have not been studied with on kidney and bone health. the emtricitabine and/ Complera, but consult with Also as a result of the TAF, or tenofovir components. a pharmacist before taking Odefsey can be taken by Monitor liver enzymes any herbals or OTC supple- people with more advanced closely in people co-infect- ments). Rifabutin must kidney disease, down to a ed with hepatitis B and, if be taken with an extra renal function (CrCL) of 30 appropriate, initiation of Edurant tablet in addition mL/min. positivelyaware.com/complera POSITIVELY AWARE MARCH+APRIL 2019 37 2019 POSITIVELY AWARE HIV DRUG GUIDE

Atripla efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) STR SINGLE-TABLET REGIMEN CONTAINING RECOMMENDED INITIAL REGIMEN AN NNRTI AND TWO NRTIs ✔ IN CERTAIN CLINICAL SITUATIONS n STANDARD DOSE • undetectable; however, DR. DAVID HARDY SAYS: Atripla was the first One tablet once daily on an empty stomach, preferably efavirenz should only be STR to be approved, in 2006. It was a popular, at bedtime (food increases the risk of central nervous used if the potential benefit heavily recommended regimen for many years, until system, or CNS, toxicities). Tablet contains 600 mg of outweighs the potential risk better STRs were approved. Due to its at times persis- the NNRTI efavirenz plus 200 mg emtricitabine and (as when other treatment tent neuropsychiatric side effects (grogginess, vivid 300 mg tenofovir disoproxil fumarate (TDF). options are not available). dreams, worsening of mental health conditions) and Because of the association elevated cholesterol, along with a requirement to be For adults and children 12 years of age and older with suicidality and neuro- taken without food and at bedtime, this STR fell out weighing at least 88 pounds (40 kg). psychiatric effects, it is also of the recommended guidelines several years ago. Take missed dose as soon as possible, unless it is recommended to screen for Clinical trials of Atripla versus integrase inhibitor-con- closer to the time of your next dose. Do not double up antenatal and postpartum taining ART regimens have shown that the integrase on your next dose. Do not split or crush the tablet. Dose depression in women with inhibitor ART regimens were superior to Atripla. cannot be adjusted for people with kidney problems and HIV who are taking a regi- Atripla is now rarely, if ever, used in the U.S.; however, Atripla should not be used in people with moderate or men containing efavirenz. it remains a commonly used ART regimen in other severe kidney or liver impairment. The efavirenz in Atripla can parts of the world (Africa, India, South America) A similar, but not exact, off-patent medication is avail- cause a false positive for although its use is decreasing. Of note, two quasi- able (see pages for Symfi and Symfi Lo, EFV/3TC/TDF). marijuana on certain drug generic, nearly-identical versions of Atripla were tests. A more specific con- approved in 2018, but their uptake has not been firmatory test can be done. strong. ➤ SEE THE INDIVIDUAL concentrating, rash, diar- DRUGS CONTAINED IN rhea, nausea, fatigue, head- n POTENTIAL DRUG INTERACTIONS ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: ATRIPLA: Sustiva and ache, and insomnia. These Do not take with Epivir- 0 Atripla is a once-a-day single-tablet regimen Truvada (co-formulation side effects may go away HBV, Hepsera, or Vemlidy that has been used to treat HIV infection for quite of Emtriva and Viread). after a few weeks. Kidney (TAF), all three used for some time. It was the favorite for initial therapy due to ➤ SEE PACKAGE INSERT for function should be assessed the treatment of hepatitis its potency and relative safety. The medicines con- more complete informa- before initiating treatment B. Atripla should not be tained in Atripla are efavirenz, emtricitabine, and tion on potential side and throughout therapy as taken with voriconazole, tenofovir disoproxil. Efavirenz is known for its neuro- effects and interactions. determined by a provider. ergot derivatives, midazol- toxicity. Individuals taking it have reported vivid Prior to initiation, people am, pimozide, triazolam, dreams, depression, fatigue, and insomnia. For some n POTENTIAL SIDE EFFECTS should be tested for hepati- bepridil, or St. John’s wort. time people believed these side effects would go AND TOXICITY tis B (HBV) infection. Severe Atripla should also not be away while others believe that you just get used to Use with caution in indi- exacerbations of hepatitis taken with other medica- them. Watch out for any liver, kidney, bone, or mental viduals with depression or B have been reported in tions that prolong QTc inter- problems while taking this regimen. Make sure your other psychiatric issues who people who are co-infected val (a heart problem) or doctor monitors you closely. are not receiving mental with hepatitis B and have medications with a known health care. A 2014 study discontinued the emtri- risk of torsades de pointes. (reference online) reviewed citabine and/or tenofovir No dose adjustment of n MORE INFORMATION n MANUFACTURER four previously published components. Monitor liver Atripla needed with Sovaldi. Atripla is listed as a Bristol-Myers Squibb AIDS Clinical Trials Group enzymes closely in people Use caution when adminis- “Recommended Regimen in bms.com (ACTG) studies regarding co-infected with hepatitis tering Atripla with Harvoni Certain Clinical Situations” atripla.com efavirenz and suicidal ide- B and, if appropriate, ini- and monitor renal function in the DHHS guidelines (800) 321-1335 ation and re-emphasized tiation of anti-hepatitis B closely due to possible based on a high rate of the fact that efavirenz has therapy may be warranted. increased tenofovir levels. central nervous system Gilead Sciences, Inc. an association with sui- The efavirenz component of Increase dose of Daklinza side effects and a possible gilead.com cidality (reported suicidal Atripla has been associated to 90 mg when used with association with suicidality. (800) GILEAD-5 ideation or attempted or with central nervous system Atripla. Atripla should not Be careful when stopping (445–3235) completed suicide), and (CNS) birth defects in non- be taken with Epclusa, Atripla, so that you avoid should be used with cau- human primates, and cases Olysio, Viekira Pak, or the rapid development of n AVERAGE WHOLESALE PRICE tion in patients with severe of neural tube defects have Zepatier. Not intended to be HIV resistance to it—check $3,266.88/month or uncontrolled depression been reported after first tri- taken with other HIV medi- with your provider or phar- and/or a history of suicid- mester exposure in humans. cations, unless prescribed macist first. ality. It is recommended A link between efavirenz that way. Tell your provider for anyone on a regimen and birth defects in humans or pharmacist about all containing efavirenz to be has not been supported in medications, herbals, and screened for depression and meta-analyses. The recom- supplements you are tak- suicidality. Common side mendation is that women in ing or thinking of taking, effects may include dizzi- their first trimester continue prescribed or not, as there ness, drowsiness, abnormal taking efavirenz as long are other drug interactions or vivid dreams, difficulty as their viral load remains which are not listed here.

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Symfi and Symfi Lo efavirenz/lamivudine/tenofovir disoproxil fumarate (EFV/3TC/TDF)

STR SINGLE-TABLET REGIMEN RECOMMENDED INITIAL REGIMEN CONTAINING AN NNRTI AND TWO NRTIs ✔ IN CERTAIN CLINICAL SITUATIONS n STANDARD DOSE as levetiracetam, should be DR. DAVID HARDY SAYS: Symfi and Symfi Lo are One tablet once daily on an• empty stomach, preferably considered. Effectiveness the ninth and tenth STRs approved by the FDA, at bedtime (food increases the risk of central nervous of birth control pills may in March 2018, and are the first fully generic STRs. Of system, or CNS, toxicities). The Symfi tablet contains be decreased; consider note, while almost identical to the branded medica- 600 mg of the NNRTI efavirenz plus 300 mg lamivudine the use of other contraception Atripla, the substitution of lamivudine for emtric- and 300 mg tenofovir DF (TDF). The Symfi Lo tablet tives. Closer monitoring and itabine (Emtriva) makes them slightly different. The contains a lower dose of efavirenz, 400 mg, plus dose adjustments may be FDA approved these two fixed-dose combinations of 300 mg lamivudine and 300 mg tenofovir DF (TDF). required with posaconazole previously approved antiretrovirals based not upon (avoid unless benefit out- clinical trial data, but rather pharmacokinetic demon- For adults and pediatric patients weighing at least weighs potential risk) and stration of bioequivalence, which means that Mylan, 77 pounds (35 kg) for Symfi Lo and 88 pounds (40 kg) itraconazole. Monitor effec- the manufacturer, had to show that the combination for Symfi. tiveness of clarithromycin or tablet of the three medications combined produced Take missed dose as soon as possible, unless it is clos- consider using azithromycin similar blood levels of the three drugs when given as er to the time of your next dose. Do not double up on your instead. Levels of immu- three separate tablets. The lower dose of efavirenz in next dose. Do not split or crush the tablet. Dose cannot nosuppressants should be Symfi Lo (400 mg) is based upon supporting data from be adjusted for people with kidney problems. Symfi and monitored when starting or the ENCORE1 study which demonstrated similar viro- Symfi Lo are not recommended for patients with CrCl less stopping Symfi or Symfi Lo. logic potency but fewer side effects with the lower than 50 mL/min or individuals requiring dialysis. Symfi or Cardizem, Lipitor, Pravachol, dose of efavirenz. The uptake of these two new fully Symfi Lo should not be used in people with moderate or and Zocor doses may need generic STRs in clinical practice is still uncertain as severe kidney or liver impairment. to be adjusted. Titrate dose both the DHHS and IAS-USA guidelines removed efa- of bupropion and sertraline virenz-containing regimens from their first-line recom- based on clinical response. mended regimens many years ago, based primarily ➤ SEE THE INDIVIDUAL B and, if appropriate, ini- Avoid use of sorbitol- upon excessive side effects compared to newer STRs. DRUGS CONTAINED IN tiation of anti-hepatitis B containing medicines with A unique and distinguishing characteristic of these SYMFI: Sustiva, Epivir, therapy may be warranted. lamivudine; there are many, STRs is their lower monthly wholesale acquisition cost and Viread. The efavirenz component such as acetaminophen (WAC): $1,630 compared to $2,100 for Delstrigo, ➤ SEE PACKAGE INSERT for in these medications can liquid (Tylenol liquid and $2,950 for Biktarvy, $3,500 for Symtuza, $2,800 for more complete informa- cause a false positive for others). No dose adjust- Triumeq, and $3,000 for Genvoya and Stribild. tion on potential side marijuana on certain drug ment of Symfi or Symfi Lo effects and interactions. tests. A more specific con- needed with Sovaldi. Use ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: firmatory test can be done. caution when administering 0 Symfi and Symfi Lo are once-daily single-tablet n POTENTIAL SIDE EFFECTS with Harvoni and moni- regimens that might offer powerful antiretroviral AND TOXICITY n POTENTIAL DRUG INTERACTIONS tor renal function closely treatment at a much lower price than comparable The most common side Do not take with Epivir- due to possible increased antiretroviral treatments on the market. The differ- effects occurring in 5% or HBV, Hepsera, or Vemlidy tenofovir levels. Increase ence between them is that Symfi Lo has a lower dose more of studied individuals (TAF), all three used for dose of Daklinza to 90 mg of efavirenz than Symfi. Research among adults living include headache (14%), treatment of hepatitis B. when used with Symfi or with HIV shows that treating them with tenofovir and body pain (13%), fever Do not take with another Symfi Lo. Should not be emtricitabine was comparably effective regardless of (8%), abdominal pain (7%), nephrotoxic (harmful to taken with Epclusa, Olysio, whether they also received 400 mg or 600 mg of efa- back pain (9%), asthenia the kidneys) medication, Viekira Pak, or Zepatier. virenz. The advantage of the lower 400 mg dose vs. (6%), diarrhea (11%), nau- such as high-dose or mul- Not intended to be taken the 600 mg higher is that the exposure to neurotoxici- sea (8%), vomiting (5%), tiple NSAIDs (non-steroidal with other HIV medications, ties is less, therefore individuals with the lower dose arthralgia (joint pain, 5%), anti-inflammatory drugs; unless prescribed that way. report less insomnia, depression, and dizziness. depression (11%), insom- these include aspirin, ibu- See Atripla page for more nia (5%), anxiety (6%), profen – Motrin, Advil, potential side effects. Tell pneumonia (5%), and rash and others, and naproxen your provider or pharma- more in African Americans. Regimen in Certain Clinical (18%). These side effects sodium – Aleve and others). cist about all medications, For individuals with HIV-2, Situations” in the DHHS are most common at the Should not be taken with herbals, and supplements commonly found in some guidelines, just as Atripla start of treatment and usu- voriconazole, ergot deriva- you are taking or thinking of other countries, an NNRTI is, due to their association ally diminish in two to four tives, midazolam, pimo- taking, prescribed or not, as would not be recom- with a high rate of central weeks. Bedtime dosing on zide, triazolam, bepridil, or there are other drug interac- mended as HIV-2 is inher- nervous system side effects an empty stomach can help St. John’s wort. Efavirenz tions which are not listed ently resistant to NNRTIs. and possible association reduce symptoms. Use should also not be taken here. Randomized clinical trial with suicidality. Be careful with caution in individuals with other medications data have demonstrated when stopping these medi- with depression or other that prolong QTc interval n MORE INFORMATION the efficacy of lower dose cations, so that you avoid psychiatric issues who are (a heart problem) or medi- Symfi and Symfi Lo are (400 mg) efavirenz found in the rapid development of not under a psychiatrist’s cations with a known risk basically alternative ver- Symfi Lo, however this dose HIV resistance to it—check care. Prior to initiation, of torsades de pointes. sions of Atripla, a well- has not been studied in a with your provider or phar- people should be tested May affect warfarin lev- established HIV medication U.S. population, in pregnant macist first. for hepatitis B (HBV) infec- els. Can decrease levels of that’s no longer in favor women, or in patients with tion. Severe exacerbations buprenorphine and metha- when starting therapy. If TB and HIV. The U.S. guide- n MANUFACTURER of hepatitis B have been done—monitor for with- you can’t sleep, ask your lines therefore preferentially Mylan reported in people who are drawal. When taken with doctor about gradually recommends Symfi with symfi.com; symfi-lo.com co-infected with hepatitis B carbamazepine, phenobar- adjusting the timing of your higher dose efavirenz (600 mylan.com and have discontinued the bital, or phenytoin, periodic dose until it’s taken during mg) over the reduced dose (877) 446-3679 lamivudine and/or tenofovir monitoring of anticonvul- the day. A rare genetic trait of efavirenz found in Symfi components. Monitor liver sant and efavirenz levels affecting drug metabolism of Lo (400 mg) at this time. n AVERAGE WHOLESALE PRICE enzymes closely in people should be done or alterna- Sustiva, leading to a higher Symfi and Symfi Lo are Symfi: $1,961.33/month co-infected with hepatitis tive anti-seizure drugs, such rate of side effects, occurs listed as a “Recommended Symfi Lo: $1,961.33/month positivelyaware.com/symfi POSITIVELY AWARE MARCH+APRIL 2019 39 2019 POSITIVELY AWARE HIV DRUG GUIDE

INVESTIGATIONAL DRUG AT PRESS TIME. "' / ' long-acting cabotegravir/rilpivirine (CAB LA/RPV LA)

PHOTO/ UNAVAILABLE LA LONG-ACTING INJECTABLE REGIMEN; DHHS RECOMMENDATION •CONTAINS AN INSTI AND AN NNRTI ● NOT YET ESTABLISHED

n STANDARD DOSE year to just 12. People who DR. DAVID HARDY SAYS: One strategy for mak- Clinical trials of this investigational regimen used a are adherent to their HIV ing ART simpler and more convenient would be long-acting cabotegravir injection of 400 mg plus 600 regimen now may be eligible to change the frequency that anti-HIV medications mg rilpivirine injection every 4 or 8 weeks. The dose to switch to this med when need to be taken or administered. Two anti-HIV medi- consisted of two 2 mL injections. Rilpivirine must be approved. The trade-off with cations have been developed into long-acting, inject- taken with food; see Edurant page for details. An induc- long-acting treatment is the able (into muscle) forms and have completed testing tion phase with oral medication was used in research requirement for near-perfect in a successful phase 2 study (LATTE-2) and are now and will be used when approved. The cabotegravir tab- adherence and visiting your in phase 3 clinical trials. Cabotegravir is an investiga- let may not otherwise be available on the market. doctor’s office 12 times a tional integrase inhibitor similar to Tivicay (dolutegra- year instead of two or three. vir). Rilpivirine is already approved by the FDA as an The treatment is also one oral anti-HIV medication (Edurant). Both have been ➤ SEE EDURANT; inhibitors (Aciphex, Dexilant, injection per butt muscle. developed into injectable forms which maintain high cabotegravir is Nexium, Prevacid, Prilosec, Cabotegravir is from the enough drug levels in the blood to suppress HIV and not yet available Protonix), or St. John’s wort. top-of-the-line HIV medica- allow for monthly or every two-months dosing. This ➤ SEE PACKAGE INSERT Antacids should be taken tions right now, the INSTI combination of co-administered (one injection of each when available for more two hours before or at least drug class. They have great drug per butt muscle) monthly or every two months complete information four hours after oral Edurant. efficacy and are, in general, regimen was studied first in a Phase 2 study called on potential side effects Acid-reducing drugs (Pepcid, easy to take. Rilpivirine is LATTE-2. In October 2018, the LATTE-2 investigators and interactions. Tagamet, Zantac, and Axid) already on the market in a reported that at 160 weeks (3 years) of follow-up, 104 should be taken 12 hours variety of oral formulations of 115 participants (90%) and 95 of 115 participants n POTENTIAL SIDE EFFECTS before or four hours after (Complera, Edurant, Juluca, (83%) receiving the injectable regimen, every 8 and 4 AND TOXICITY an oral Edurant dose. Some and Odefsey). Rilpivirine is weeks respectively, remained virally suppressed. Of In one study, injection site of these interactions will not sold separately as an the patients on the oral comparator arm who chose to reactions with mild, short- no longer be relevant once injectable. Cabotegravir is switch to the injectable regimen at week 96, 33 of 34 term (two to five days) injection therapy begins, also being studied for HIV participants (97%) and 10 of 10 participants (100%) redness, pain, and swelling or a maintenance phase prevention as one PrEP shot remained virally suppressed on every 8- and 4-week was reported in 84% of all containing rilpivirine starts; taken every two months. dosing, respectively. Building on the success of injections. Moderate symp- however, see package insert The lead-in oral dosing is LATTE-2, this injectable ART regimen is being studied toms were reported in 15% when available for guidance. used to establish the toler- for HIV treatment in two Phase 3 studies: FLAIR (treat- of injections. Less than 1% Monitor for worsening of any ability of cabotegravir prior ment-naïve) and ATLAS and ATLAS-2M (treatment- of patients discontinued fungal infections when rilpi- to long-acting injection. For experienced with ART switch in PLWH with the study due to injection virine is used with antifungal example, if an allergic reac- undetectable viral loads). Results from ATLAS-2M are site reactions. There have medications like fluconazole, tion occurs, it can be out expected in 2019. We know that the LATTE-2 showed been rare reports of depres- itraconazole, ketoconazole, of the system in a day or very good HIV suppression and few generalized side sion and suicidal ideation, posaconazole, or voricon- two. In the LATTE-2 study effects, but nearly 100% of the PLWH receiving the primarily in patients with azole; dose adjustment for with people on first-time monthly or two-monthly injections in their butt mus- a history of psychiatric ill- these medications may be HIV therapy, cabotegravir cles reported mild, short-term (2–5 days) “injection nesses, in people receiving needed. Use azithromycin plus rilpivirine given every site reactions,” consisting of pain, redness, and swell- INSTI-based regimens. The when possible instead of 4 weeks or every 8 weeks ing where they received the injections. Interestingly, DHHS guidelines recom- the antibiotics clarithro- was found to be as effective the majority of PLWH in the study preferred the injec- mend closely monitoring mycin, erythromycin, or as the traditional three-med tions over their previous daily tablet ART regimens. patients with pre-existing telithromycin. Methadone (even if only as one pill) oral This was reported to be due to greater convenience of psychiatric conditions on an levels are reduced slightly combination given to people monthly or two-monthly dosing, lack of being remind- INSTI. There may be a pos- and patients should be in the control group of the ed daily of their HIV-positive status, and not having to sibility of birth defects—see monitored for symptoms of trial. There was some viro- remember and manage tablet prescriptions. More will “More information.” withdrawal. Should be used logic failure in the 8 week be revealed regarding this new way of receiving ART with caution when taken group vs. none in the 4 as results from the studies above become available. n POTENTIAL DRUG INTERACTIONS with other medications with week; hence, research went [See more data online.] It is important to note that New interactions continue a known risk of torsades forward with only 4 week injectable cabotegravir given every two months by to be discovered after drug de pointes or QT prolonga- dosing. This success was itself is also being compared to Truvada for pre-expo- approval (cabotegravir is tion (these abnormal heart out to 96 weeks (nearly two sure prophylaxis (PrEP) in two large studies being con- the new medication). Not rhythms can make the years). Moreover, the major- ducted by the HIV Prevention Trials Network (HPTN). intended to be taken with heart stop). Tell YOUR pro- ity of participants given other HIV medications, vider or pharmacist about shots in the Phase III ATLAS ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: unless prescribed that all medications, herbals, study (more than 96%) said 0 A few long-acting HIV regimens are under way. If used with abacavir/ and supplements you are they preferred the injections investigational. These regimens will change HIV care lamivudine during the initial taking or thinking of taking, every month or two months radically and further on will do so with PrEP as well. oral induction phase, as this prescribed or not, as there to taking their previous daily The ATLAS study showed long-acting cabotegravir regimen was also studied, are other drug interactions HIV oral regimen, despite and rilpivirine, injected once a month, had similar effi- be aware of possible drug which are not listed here. any side effect or injection cacy to a standard of care, daily, oral three-drug regi- interactions with these site reaction. New prelimi- men at week 48. This study was designed for agents (see Epzicom page). n MORE INFORMATION nary data from an obser- individuals on HIV treatment that were virally sup- During the initial oral induc- May be FDA approved this vational study in Botswana pressed for at least six months. tion phase with rilpivirine, it year. This drug is taken once suggest that there may be is not recommended to co- a month, as two shots, into an increased risk of birth administer carbamazepine, the muscle. That’s it. Or as defects in infants born to n MANUFACTURER n AVERAGE WHOLESALE PRICE oxcarbazepine, phenobar- ViiV Healthcare pointed out, those who were receiving ViiV Healthcare Not yet established. bital, phenytoin, rifampin, it changes HIV treatment dolutegravir at the time of viivhealthcare.com rifapentine, proton pump from 365 dosing days per conception. (877) 844-8872

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Tivicay dolutegravir (DTG) INSTI INTEGRASE STRAND RECOMMENDED AS COMPONENT TRANSFER INHIBITOR ★ OF INITIAL REGIMEN FOR MOST PEOPLE n STANDARD DOSE • people with confirmed DR. DAVID HARDY SAYS: Tivicay was the third One 50 mg tablet once daily without regard to food, for or suspected INSTI drug integrase inhibitor approved, in 2013, initially as people on HIV therapy for the first time (treatment- resistance, but these medi- a single agent and a year later as a component of the naïve) or treatment-experienced people who have cations can be taken with STR Triumeq (Tivicay/Ziagen/Epivir). What makes never taken an INSTI. One 50 mg tablet twice daily, Tivicay 50 mg twice daily. Tivicay stand out from other integrase inhibitors or without regard to food, for people who have or who are Should be okay to take with STRs containing integrase inhibitors is its proven high suspected to have certain INSTI drug resistance or who Daklinza, Epclusa, Harvoni, barrier to HIV resistance. To date (more than five are taking certain other medications. Must be taken in Olysio, Sovaldi, Viekira Pak, years since initial approval), there have been few, if combination with another antiretroviral(s) which does or Zepatier. Tell your pro- any, well-confirmed cases of resistance to Tivicay in not contain this medication or medication from the vider or pharmacist about PLWH taking this medication as first-time ART. In same drug class. all medications, herbals, addition, clinical trial data show that Triumeq is supe- and supplements you are rior to (better than) Atripla and both Prezista/Norvir Tivicay is approved for adults and children weighing taking or thinking of taking, and Reyataz/Norvir in terms of suppressing viral at least 66 pounds (30 kg). For patients weighing prescribed or not, as there loads as well as having fewer side effects. As men- 66 pounds (30 kg) to 88 pounds (40 kg), the dose is are other drug interactions tioned before, many HIV treaters are not always com- one 10 mg tablet and one 25 mg tablet (35 mg total which are not listed here. fortable with prescribing Triumeq due to the Ziagen dose) once daily without regard to food. For patients (abacavir) which it contains for reasons mentioned on weighing at least 88 pounds (40 mg), the dose is one n MORE INFORMATION other pages. For those treaters, the two-pill combina- 50 mg tablet once daily without regard to food. Tivicay is part of Juluca as tion of Tivicay and Descovy has become their favorite Take missed dose as soon as possible, unless it is clos- well as Triumeq, both sin- “go-to” first-line ART regimen. How this is now changer to the time of your next dose. Do not double up on your gle-tablet regimens. Tivicay ing with the availability of Biktarvy is not yet clear. next dose. Not recommended for people with severe liver is considered a second- Some HIV treaters and the PLWH for whom they pre- impairment. Use with caution in people with severe kidney generation INSTI—it may scribe antiretrovirals may opt to simplify to Biktarvy impairment who have INSTI drug resistance or suspected work in many individuals or stick with what is already working well. In 2018, resistance, because Tivicay levels may be decreased. whose virus has developed preliminary results from the Tsepamo study from resistance to other INSTIs, Botswana unexpectedly showed an increased occur- but it needs to be dosed rence of neural tube defects in infants of HIV-positive ➤ SEE PACKAGE INSERT for people with hepatitis B or C. twice daily in these people. women who were taking Tivicay at the time of con- more complete informa- There may be a possibility Compared to other INSTIs, ception. Until the final results of this study are known tion on potential side of birth defects—see “More Tivicay has a high genetic sometime in 2019, the use of Tivicay in HIV-positive effects and interactions. information.” barrier against the develop- women desiring to become pregnant and those able ment of resistance, similar to become pregnant who are not using contraception n POTENTIAL SIDE EFFECTS n POTENTIAL DRUG INTERACTIONS to the protease inhibitors is recommended to be avoided (see Triumeq). AND TOXICITY Do not take with the (such as Prezista). Tivicay In general, Tivicay is well anti-arrhythmic dofetilide. has also demonstrated ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: tolerated with infrequent Intelence decreases Tivicay superiority to Prezista when 0 Tivicay is approved once a day for HIV-positive side effects. The most com- levels by 88%, therefore, looking at virologic results. individuals initiating HIV treatment for the first time mon moderate to severe these two medications must Pediatric HIV guidelines and for those on HIV treatment who have not taken side effects in clinical stud- be co-administered with added Tivicay as part of a integrase inhibitors before. It is prescribed twice a ies were insomnia (3%), Kaletra, boosted Prezista, preferred regimen. Tivicay day, however, for those who have developed resis- headache (2%), and fatigue or boosted Reyataz. Tivicay is particularly useful when tance to other integrase inhibitors. (2%). Mild insomnia was should be taken two hours drug interactions are a con- seen in 7% of participants before or six hours after cern with the HIV protease in one study. Additionally, taking laxatives or antac- inhibitor (PI) drugs. Tivicay increased CPK (creatine ids, the ulcer medication is a small tablet, a benefit participants. Another strat- are pregnant or within 12 kinase, a lab value indicat- sucralfate, oral iron or for patients who have dif- egy with some supporting weeks of conception. It is ing muscle damage), rhab- calcium supplements, or ficulty swallowing. evidence suggests switching unclear whether dolute- domyolysis (breakdown of buffered medications. It Tivicay as part of Juluca patients with a suppressed gravir is the only integrase muscle), and myopathy or can be taken with iron- or is used as a medication to viral load to a regimen of inhibitor with the potential myositis (muscle pain) were calcium-containing supple- switch to for people with Tivicay + Epivir (lamivu- to cause these birth defects reported. There have been ments if taken together with undetectable viral loads on dine, 3TC) for maintenance (neural tube defects), or if rare reports of depression food. Acid reducers (Pepcid, their current regimen for at therapy. A fixed-dose com- other integrase inhibitors and suicidal ideation, pri- Zantac, Tagament) and least six months; see Juluca. bination pill with these two also carry this risk. Consult marily in patients with a his- proton pump inhibitors (for Another ART (antiretroviral medications is expected to your provider to discuss tory of psychiatric illnesses, example, Aciphex, Dexilant, therapy) switch strategy be approved this year; see guidance on how to manage in people receiving INSTI- Prilosec, Prevacid, Protonix, with some supporting evi- dolutegravir/3TC page. regimens containing dolute- based regimens. The DHHS and Nexium) are okay to dence for its consideration New preliminary data gravir or a different inte- guidelines recommend use. Avoid taking with in people with viral suppres- from an observational study grase inhibitor if there is any closely monitoring patients Viramune, oxcarbazepine, sion in the DHHS guidelines in Botswana suggest that possibility of conception. on an INSTI who have pre- phenytoin, phenobarbital, that uses Tivicay is switch- there may be an increased existing psychiatric condi- and St. John’s wort. Start ing to a boosted protease risk of birth defects in n MANUFACTURER tions. Tivicay can cause a metformin at lowest dose inhibitor + integrase inhibi- infants born to those who ViiV Healthcare small, reversible increase in and titrate based on gly- tor. In two small observa- were receiving dolutegravir viivhealthcare.com kidney function test (serum cemic control. Monitor for tional studies, individuals at the time of conception. tivicay.com creatinine) within the first metformin adverse effects. were switched from their Until more information is (877) 844-8872 few weeks of treatment Use alternatives to rifampin, current ART regimens to available, regimens con- without affecting actual kid- carbamazepine, efavirenz, Prezista + Norvir + Tivicay, taining dolutegravir are not n AVERAGE WHOLESALE PRICE ney function. Liver enzymes Aptivus/Norvir, and Lexiva/ and viral suppression was recommended for use in 50 mg tablets: should be monitored in Norvir when possible in maintained in over 97% of ART-naïve patients who $2,088.59/month positivelyaware.com/tivicay POSITIVELY AWARE MARCH+APRIL 2019 41 2019 POSITIVELY AWARE HIV DRUG GUIDE

Isentress HD (and Isentress) raltegravir (RAL) INSTI INTEGRASE STRAND RECOMMENDED AS COMPONENT TRANSFER INHIBITOR ★ OF INITIAL REGIMEN FOR MOST PEOPLE n STANDARD DOSE • carbamazepine or pheno- DR. DAVID HARDY SAYS: Isentress HD was ISENTRESS HD: Two 600 mg film-coated tablets once barbital. Raltegravir can be approved by the FDA in May 2017. It was devel- daily for individuals new to HIV therapy (treatment- used with Daklinza, Harvoni, oped to offer PLWH the option for a once-daily naïve) or who are virologically suppressed (have Olysio, Sovaldi, Viekira Pak, Isentress regimen. The total daily Isentress dose is undetectable viral load) on an initial regimen of Zepatier, or Epclusa. Unlike 1,200 mg/day (600 mg x 2) along with two NRTIs (one Isentress. Isentress, Isentress HD can- tablet of Truvada, Epzicom, or Descovy). It’s hard to not be used with Intelence imagine what the advantage of taking two Isentress ISENTRESS: One 400 mg film-coated tablet twice daily or boosted Aptivus. Tell HD plus another pill, all once-daily, would be over tak- for people with HIV treatment experience; this Isentress your provider or pharma- ing one of the STRs. Isentress was the first integrase dose may also be taken by those new to HIV therapy. cist about all medications, approved, in 2007. Initially, it has to be taken twice herbals, and supplements daily (two tablets 8–12 hours apart). Early clinical tri- Must be taken in combination with another antiretroviral(s) you are taking or thinking of als demonstrated very rapid (and still the most rapid) which does not contain this medication or medication taking, prescribed or not, as drops in viral loads (compared to protease inhibitor from the same drug class. Isentress HD is for adults and there are other drug interac- and NNRTI regimens), suggesting that it was more children weighing at least 88 pounds (40 kg). Isentress is tions which are not listed potent than older classes of antiretrovirals. However, for adults and children weighing at least 4 pounds (2 kg). here. we soon learned that this rapid drop in viral load did Both Isentress HD and Isentress can be taken without not correlate with resistance to HIV resistance, as regard to food. n MORE INFORMATION this occurs with Isentress at a rate similar to that for Isentress (but not Isentress HD) pediatric formulations The newer formulation of Atripla. At the time when Isentress was approved, it are available as oral granules for suspension and flavored Isentress HD was approved provided a critical new medication for many PLWH chewable tablets. Isentress dosing for neonates (birth to in 2017. While the previous who had run out of treatment options and kept them 4 weeks [28 days] of age) (for oral granules for suspen- version, Isentress, was well alive. Isentress is one of, if not, the antiretrovirals sion) and children less than 55 pounds (for chewable tolerated and highly effec- with the fewest side effects. With the development of tablets) is based on weight; see package insert for dos- tive, its twice-daily dose newer once-daily integrase inhibitors (Tivicay) and ing. The chewable tablets may be chewed or swallowed was seen by some as a STRs (Genvoya, Biktarvy), the use of Isentress has whole. Do not substitute chewable tablets or oral suspen- small hindrance. Raltegravir- waned in favor of simpler ART regimens. sion for film-coated tablets. based regimens may be Take missed dose as soon as possible, unless it’s preferred for patients with ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: closer to the time of your next dose. Do not double up high cardiovascular risk. 0 Isentress and Isentress HD are both the brand on your next dose. Isentress is the preferred names for the integrase inhibitor known as raltegra- INSTI medication in HIV vir. It is prescribed to treat HIV infection in patients treatment guidelines for with multi-drug resistance who have not taken inte- ➤ SEE PACKAGE INSERT for with pre-existing psychiat- pregnancy, 400 mg twice grase inhibitors before, as well as for individuals initi- more complete informa- ric conditions on an INSTI. a day in combination with ating treatment for the first time. The differences tion on potential side Chewable tablets contain 2 NRTIs. In pediatric HIV between regular Isentress and the HD version are the effects and interactions. phenylalanine, which can guidelines, Isentress was contained dose and the frequency that it is taken. be harmful to patients with downgraded in 2017 from With regular Isentress, you take one 400 mg pill twice n POTENTIAL SIDE EFFECTS phenylketonuria. “preferred” to an “alternative” a day, while with Isentress HD you take two 600 mg AND TOXICITY part of an initial regimen last pills once a day. Isentress (not HD) can also be pre- In general, raltegravir is n POTENTIAL DRUG year for children ages 6–12. scribed to children as an oral suspension or as chew- very well tolerated with INTERACTIONS New preliminary data able tablets. If a skin rash or an allergic reaction infrequent side effects. Isentress HD cannot be from an observational study develops, stop the drug and call your provider. Liver Those reported in up to used with rifampin, but in Botswana suggest that and kidney functions must be monitored. 3–4% of study subjects Isentress can; increase there may be an increased include insomnia, nausea, Isentress to 800 mg twice risk of birth defects in and headache. The side daily when using with infants born to those who effect profile in children rifampin. Remember to were receiving dolutegravir is comparable to adults. decrease the raltegravir at the time of conception. It Isentress may cause elevat- back to its original dose is unclear if other integrase ed levels of creatine kinase when you finish taking inhibitors also carry this (a muscle enzyme). Inform rifampin. There are no data risk. Consult your provider your provider or pharma- on dosing of the chewable to discuss guidance on how cist if you have a history of tablets with rifampin. There to manage regimens con- rhabdomyolysis, myopathy, is no need to increase the taining dolutegravir or a or increased creatine kinase, raltegravir dose with rifabu- different integrase inhibitor or if you also take medica- tin. With both Isentress if there is any possibility of tions that may contribute HD and Isentress, avoid conception. to these conditions such as Gaviscon and other antac- statins, fenofibrate, or gem- ids containing aluminum n MANUFACTURER fibrozil (cholesterol medica- or magnesium. Calcium- Merck and Co. tions). There have been rare containing antacids like isentresshd.com reports of depression and Tums (calcium carbon- isentress.com suicidal ideation, primarily ate) can be used with (800) 622–4477 in patients with a history Isentress, but not Isentress of psychiatric illnesses, in HD. Other acid reducers n AVERAGE WHOLESALE PRICE people receiving INSTI- (such as Pepcid, Zantac, Isentress HD: based regimens. The DHHS Prilosec, and Prevacid) are $1,800/month guidelines recommend okay to use. Raltegravir Isentress 400 mg: closely monitoring people is not recommended with $1,800/month

42 MARCH+APRIL 2019 POSITIVELY AWARE positivelyaware.com/isentresshd 2019 POSITIVELY AWARE HIV DRUG GUIDE

Prezcobix darunavir/cobicistat (DRV/COBI) FIXED-DOSE COMBINATION CONTAINING PI/PKE A PROTEASE INHIBITOR AND A PHARMACOKINETIC RECOMMENDED AS COMPONENT OF INITIAL REGIMEN ENHANCER (BOOSTER) ✔ IN CERTAIN CLINICAL SITUATIONS n STANDARD DOSE • many drugs because, as DR. DAVID HARDY SAYS: Approved in early 2015, One tablet (800 mg of the PI darunavir boosted by a booster, it inhibits liver this two-drug tablet consolidated Prezista and 150 mg cobicistat) once daily with food, in people with enzymes involved in drug the booster Tybost into one tablet. It assures that no darunavir-associated drug resistance, including metabolism. Do not take Prezista will always be taken with its necessary boost- both treatment-experienced individuals and those with betamethasone, er. It has the “distinction” of being the largest antiret- who are treatment-naïve (taking HIV therapy for the budesonide, carbamaze- roviral tablet, which may be a problem for some first time). Must be taken in combination with another pine, ciclesonide, dexameth- PLWH to swallow. It was developed not only to ensure antiretroviral(s) which does not contain the medica- asone, dronedarone, ergot boosting and reduce pill number, but also as part of tions in this drug or medication from the same drug derivatives, eslicarbazepine, the run-up to the development of Symtuza. Its side classes. Use with non-nucleosides or other protease fluticasone, triazolam, oral effects are identical to those mentioned in Prezista. inhibitors is not recommended. midazolam, lomitapide, lurasidone, methylpred- ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: Prezcobix is only available for people taking darunavir nisolone, mometasone, 0 This is a protease inhibitor (PI) combined in one once daily, not those who require darunavir twice daily. oxcarbazepine, phenobar- tablet with the booster known as cobicistat (COBI). It is not recommended to co-administer Prezcobix with bital, phenytoin, pimo- Because of COBI, this PI can be taken once a day tenofovir disoproxil fumarate (brand name Viread, found in zide, rivaroxaban, Revatio, and should be used in combination with other HIV Truvada), with creatinine clearance (CrCl) less than simvastatin, lovastatin, St. medicines. This protease inhibitor is superior in 70 mL/min (a measure of kidney function). John’s wort, triamcinolone, efficacy and tolerability when compared to Kaletra Take missed dose as soon as possible, unless it is alfuzosin, ranolazine, or (lopinavir/ritonavir), another boosted PI. Darunavir closer to the time of your next dose. Do not double up rifampin. Not recommend- is lipid-friendly and less likely to cause metabolic on your next dose. Prezcobix is not recommended during ed to be taken with avanafil, complications. If prescribed with Truvada, it is pregnancy due to substantially lower exposures of daruna- everolimus, rifapentine, sal- important to then monitor kidney functions and bone vir and cobicistat during pregnancy. Cobicistat has not meterol, ticagrelor, or vori- density. As with the other protease inhibitors, been studied in individuals under 18 years of age, thus conazole. Apixaban dose darunavir is metabolized by the liver; many drug-drug Prezcobix should not be used in pediatric patients. Do not may need to be adjusted. interactions can occur, either increasing or decreasing use in people with severe liver impairment. Beclomethasone, pred- drug levels, causing serious problems. Your doctor nisolone, and prednisone must be aware of all the medications you take, even as alternative corticoste- if they are over-the-counter or supplements. ➤ SEE THE INDIVIDUAL should also be monitored. riods may be considered, DRUGS CONTAINED IN Kidney impairment, includ- particularly for long-term PREZCOBIX: Prezista ing cases of acute kidney use. Atorvastatin and rosu- A single-tablet, once-daily n MANUFACTURER and Tybost. failure and Fanconi syn- vastatin dose should not regimen containing daruna- Janssen Therapeutics ➤ SEE PACKAGE INSERT for drome, has been reported exceed 20 mg daily. Clinical vir/COBI/FTC/TAF is now prezcobix.com more complete informa- in patients taking both cobi- monitoring is recommended available (see Symtuza). (800) JANSSEN tion on potential side cistat and Viread (tenofovir with drospirenone, due to Darunavir is recommended (526-7736) effects and interactions. DF or TDF, also found in potential for hyperkalemia. as part of an initial regimen Truvada). When used with Do not take with colchicine “in certain clinical situa- n AVERAGE WHOLESALE PRICE n POTENTIAL SIDE EFFECTS TDF, a baseline CrCl, urine if there is kidney or liver tions” in DHHS guidelines. $2,317.55/month AND TOXICITY glucose, and urine protein is impairment. Can be used DHHS wrote this is “in part As darunavir (contained in needed; CrCl, urine glucose, with Daklinza. Cannot be because of greater toler- Prezcobix) contains a sulfa and urine protein should be taken with Zepatier. Based ability” with the integrase component, patients with a monitored regularly while on the mechanism, drug inhibitor medications com- known sulfonamide allergy taking Tybost-containing interactions with other pared to Prezista + Norvir should be monitored for regimens. While very rare, hepatitis C medications or Prezcobix. According to rash after starting it. The severe rash (in 0.4% of are probably similar to the the guidelines, “An example most common side effects those taking it), accompa- interactions with Prezista of a situation in which a reported in at least moder- nied in some cases by fever + Norvir. Tell your provider darunavir-based regimen ate intensity in 5% or more and/or elevations of AST/ or pharmacist about all may still be preferred is of study participants were ALT (liver enzymes), can medications, herbals, and when a high genetic barrier diarrhea, nausea, rash, be life-threatening. Seek supplements you are taking to resistance is particularly headache, abdominal pain, medical attention immedi- or thinking of taking, pre- important, such as when and vomiting. Cobicistat ately. Observational cohort scribed or not. there is substantial concern can cause a small, revers- studies reported an asso- regarding a person’s adher- ible increase in serum creat- ciation between some PIs n MORE INFORMATION ence or when antiretroviral inine (SCr, which indicates (including darunavir) and an Since Prezista (darunavir) therapy (ART) should be the eGFR or estimated CrCl increased risk of cardiovas- must be used with a PK initiated before resistance lab values) within the first cular (CV) events. Although enhancer such as cobicistat test results are available few weeks of treatment some older PIs have been or ritonavir, this formulation [go to aidsinfo.nih.gov].” without affecting actual kid- associated with liver toxic- makes for greater conve- Examples of people needing ney function (see Tybost for ity, lactic acidosis, diabe- nience, one less pill, and to start treatment immedi- more information). Patients tes, or fat redistribution, one less co-pay. The result- ately before resistance test experiencing a confirmed these conditions are only ing co-formulation, however, results are available include increase in serum creati- rarely, or never, seen with is rather large in size, but newly infected individuals, nine of greater than 0.4 mg/ darunavir. With PIs, there the tablets are designed pregnant women, and those dL from baseline should be can be increased bleeding as an immediate-release who are experiencing cer- closely monitored for renal in hemophiliacs. formulation, so no potential tain opportunistic infections safety. Serum phosphorus problem with absorption is (an indication of advanced in patients with or at risk n POTENTIAL DRUG INTERACTIONS anticipated if the tablets are disease). for kidney impairment Cobicistat interacts with chewed, split, or crushed. positivelyaware.com/prezcobix POSITIVELY AWARE MARCH+APRIL 2019 43 2019 POSITIVELY AWARE HIV DRUG GUIDE

Prezista darunavir (DRV) PI PROTEASE RECOMMENDED AS COMPONENT OF INHIBITOR ✔ INITIAL REGIMEN IN CERTAIN CLINICAL SITUATIONS n STANDARD DOSE • as fentanyl and oxycodone. DR. DAVID HARDY SAYS: Approved in 2006, it is One 800 mg tablet with 100 mg Norvir or 150 mg Monitoring of clonazepam still the “newest” protease inhibitor (this tells Tybost once daily with food for treatment-naïve is recommended. Reduced you something about recent progress in this class of people (those taking HIV therapy for the first time) and dose of rifabutin is rec- medications). It must always be given with a booster, treatment-experienced adults without Prezista-related ommended. Do not use Norvir (ritonavir) or Tybost (cobicistat), to be effec- resistance. One 600 mg tablet with 100 mg Norvir lovastatin or simvastatin, tive. It is approved to be given as a part of a first-time twice daily with food for pregnant women and those or co-formulations contain- ART regimen dosed once-daily (800 mg tablet + who have at least one Prezista-related resistance ing these drugs (Advicor booster) with two NRTIs or dosed twice-daily (600 mg mutation. Prezista should always be taken with Norvir and Vytorin). Cholesterol- tablet + booster) for PLWH whose HIV has some resis- or Tybost. Must also be taken in combination with lowering alternatives are tance to protease inhibitors. Its major side effects are another antiretroviral(s) which does not contain this rosuvastatin, atorvastatin nausea, queasiness, diarrhea, and rash. It is the first medication or medication from the same drug class. (should not exceed 20 mg and only protease inhibitor which is now approved as per day), pitavastatin, and part of an STR (see Symtuza). For adults and children 3 years of age and older weigh- pravastatin, but should ing at least 22 pounds (10 kg). be used with caution ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: Prezista for children is dosed based on weight. There and started at the lowest 0 Darunavir is lipid-friendly and less likely to are 75 mg and 150 mg tablets as well as an oral suspen- dose possible. Monitor cause metabolic complications. If prescribed with sion (100 mg/mL) (strawberry cream flavor) available for for increased side effects Truvada, it is important to monitor kidney function children three and older and adults who can’t swallow pills. from these medications. and bone density. As with the other protease inhibitors, Suspension needs to be taken with Norvir or Tybost, Reduce clarithromycin dose darunavir is metabolized by the liver; many drug-drug with food. by 50 to 70% in kidney interactions can occur either increasing or decreasing Take missed dose as soon as possible, unless it is impairment. The antifungal drug levels, causing serious problems. Your doctor closer to the time of your next dose. Do not double up drugs itraconazole or keto- must be aware of all the medications you take even on your next dose. conazole should be used if they are over-the-counter or supplements. with caution (maximum dose is 200 mg per day ➤ SEE PACKAGE INSERT for (including darunavir) and an for either). Voriconazole prescribed or not, as there boosted protease inhibitor more complete informa- increased risk of cardiovas- should not be used unless are many other drug interac- + integrase inhibitor. In two tion on potential side effects and interactions. cular (CV) events. Although the benefits outweigh the tions not listed here. small observational stud- some older PIs have been risks. Prezista increases ies, patients were switched associated with liver toxic- levels of nasal and inhaled n MORE INFORMATION from their current ART regi- n POTENTIAL SIDE EFFECTS ity, lactic acidosis, diabe- fluticasone (found in Advair, Prezista, which is now mens to Prezista + Norvir AND TOXICITY tes, or fat redistribution, Flonase, Breo Ellipta, found in the recently + Tivicay, and viral suppres- Prezista contains a sulfa these conditions are only Arnuity Ellipta, and Flovent) approved single-tablet sion was maintained in over component and should rarely, or never, seen with and budesonide, as well regimen Symtuza (see that 97% of participants. For be used with caution in darunavir. IRIS (immune as systemic corticosteroids page), is recommended as patients on a complicated patients with severe sulfa reconstitution inflamma- ciclesonide, betamethasone, part of an initial regimen salvage regimen with cur- allergies. Most common tory syndrome) may occur dexamethasone, methyl- “in certain clinical situa- rent viral suppression and a side effects may include as the immune system prednisolone, mometasone, tions” in DHHS guidelines. history of treatment failure, diarrhea, nausea, head- regains strength; signs and and triamcinolone. Use DHHS wrote this is “in part there is evidence to support ache, rash, vomiting, and symptoms from previous alternative corticosteroid because of greater toler- simplifying the regimen to abdominal pain. Measure infections may occur soon and monitor for signs ability” with the integrase a combination of Genvoya liver function before starting after HIV treatment is initi- of Cushing’s syndrome. inhibitor medications com- + Prezista. A single-tablet, and then monitor, with per- ated. Report symptoms of Beclomethasone, pred- pared to Prezista + Norvir once-daily regimen contain- haps closer monitoring for illness, such as shingles or nisolone, and prednisone as or Prezcobix. There is growing darunavir/COBI/FTC/ those with underlying liver TB, to a health care provid- alternative corticosteriods ing evidence that a protease TAF is now available (See problems, especially during er. Protease inhibitors can may be considered, par- inhibitor-based regimen, Symtuza). Prezista + Norvir the first several months. No cause increased bleeding in ticularly for long-term use. boosted by ritonavir plus is a preferred component in dose adjustment necessary hemophiliacs. Effectiveness of oral contra- Epivir (lamivudine), can the DHHS perinatal guide- with mild to moderate liver ceptives may be decreased; maintain viral suppression lines for use in pregnancy. disease, but Prezista + n POTENTIAL DRUG INTERACTIONS consider using alternative in patients who initiated Prezista is also found in the Norvir is not recommended Drug interactions of methods of contracep- triple-drug therapy, who fixed-dose tablet Prezcobix. for those with severe liver Prezista + Norvir may tion. Monitoring is recom- achieved sustained viral impairment. While very rare, be different than those mended with methadone. suppression for at least n MANUFACTURER severe rash (in 0.4% of for Prezista + Tybost. Do Titration or decreased dose 1 year, and who have no Janssen Therapeutics those taking it), accompa- not take with alfuzosin, may be needed for buspi- evidence of, or risk of resis- prezista.com nied in some cases by fever dronedarone, colchicine (in rone, diazepam, estazolam, tance to, either darunavir or (800) JANSSEN and/or elevations of AST/ patients with kidney or liver and zolpidem. Therapeutic lamivudine. Use of Prezista (526-7736) ALT (liver enzymes), can be impairment), lomitapide, drug monitoring is recom- with Norvir and Epivir may life-threatening. Seek medi- lurasidone, ranolazine, mended for antiarrhythmics be a reasonable option n AWP cal attention immediately. pimozide, ergot derivatives, amiodarone, bepridil, diso- when the continued use of 800 mg tablets: When used with Tybost a triazolam, oral midazolam, pyramide, flecainamide, TDF, TAF, or ABC is contra- $2,027.65/month small increase in serum cre- rifampin, Revatio, Xarelto, systemic lidocaine, mexi- indicated or not desirable. atinine (SCr) may be seen or St. John’s wort. letine, propafenome, and Additionally, another ART which does not translate to Tramadol dose decrease quinidine. Tell your provider switch strategy with some a decrease in kidney func- may be needed. Monitor or pharmacist about all supporting evidence in tion. Observational cohort therapeutic effects and medications, herbals, and patients with viral suppres- studies reported an asso- adverse reactions with use supplements you are tak- sion in the DHHS guidelines ciation between some PIs of some analgesics, such ing or thinking of taking, is to switch patients to a

44 MARCH+APRIL 2019 POSITIVELY AWARE positivelyaware.com/prezista 2019 POSITIVELY AWARE HIV DRUG GUIDE

Evotaz atazanavir/cobicistat (ATV/COBI) FIXED-DOSE COMBINATION CONTAINING PI/PKE A PROTEASE INHIBITOR AND A RECOMMENDED AS COMPONENT OF PHARMACOKINETIC ENHANCER (BOOSTER) ✔ INITIAL REGIMEN IN CERTAIN CLINICAL SITUATIONS n STANDARD DOSE • n POTENTIAL DRUG INTERACTIONS DR. DAVID HARDY SAYS: Approved in early 2015 One tablet once daily with food. Each tablet con- Cobicistat interacts with (at the same time as Prezcobix), this two-drug tains 300 mg of atazanavir boosted by 150 mg many drugs, because as tablet combines Reyataz with a booster (Tybost) to cobicistat. Must be taken in combination with a booster it inhibits liver ensure boosting and reduce pill number. There is and another antiretroviral(s) which does not contain the enzymes involved in drug will not be (any time soon) an STR containing medications in this drug or medication from the same metabolism. Do not take Reyataz. As discussed on the Reyataz page, the use drug classes. Use with Intelence or Sustiva is not with ergot derivatives, tri- of Reyataz as a first-time regimen for PLWH has sig- recommended. azolam, oral midazolam, nificantly decreased due to its increased side effects lurasidone, pimozide, compared to other ART options. Use in treatment-experienced patients depends on Revatio, simvastatin, lov- protease inhibitor drug resistance. Co-administration with astatin, St. John’s wort, ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: drugs containing tenofovir disoproxil fumarate (Viread, Viramune, alfuzosin, ranola- 0 Evotaz is atazanavir boosted with cobicistat, found in Atripla, Cimduo, Complera, Delstrigo, Stribild, zine, rifampin, dronedarone, and is prescribed for treatment-experienced patients Symfi, Symfi Lo, and Truvada) is not recommended if kid- or irinotecan. Do not take and those initiating HIV treatment for the first time. ney function as measured by creatinine clearance is below with colchicine if there is Evotaz is a once-a-day, single-tablet two-drug treat- 70 mL/min. Co-administration with drugs containing teno- kidney or liver impairment. ment for use in combination with other HIV medi- fovir alafenamide (Vemlidy, found in Biktarvy, Descovy, Do not use with Olysio, cines. Compared to previous PIs, it has a friendly lipid Genvoya, Odefsey, and Symtuza) is not recommended if Viekira Pak, or Zepatier. profile, eliminating any worries about metabolic com- kidney function as measured by creatinine clearance is Can be used with Sovaldi, plications. Even though cobicistat is not clinically below 30 mL/min. Daklinza (reduce Daklinza inferior to boosting with ritonavir, as a single-tablet Not recommended in people with any degree of liver dose to 30 mg), or Harvoni dual therapy it makes treatment easier for individuals impairment or those who are treatment-experienced and (if TDF is not part of the by eliminating one pill and an extra co-payment. on hemodialysis. HIV regimen). Monitor for AbbVie, the maker of ritonavir, never licensed ritona- Take missed dose as soon as possible, unless it is tenofovir toxicities with vir to be used in a co-formulation with other HIV closer to the time of your next dose. Do not double up on Epclusa if TDF is part of drugs. Drug interactions are a concern. Acid reflux your next dose. Evotaz is not recommended during preg- the regimen. Tell your pro- medications can interfere with the absorption of ata- nancy due to substantially lower exposures of atazanavir vider or pharmacist about zanavir. With atazanavir there is an increase of biliru- and cobicistat during pregnancy. Cobicistat has not been all medications, herbals, bin that, although not harmful, causes yellowing of studied separately from Genvoya and Stribild in individuals and supplements you are the eyes and skin. Watch the kidneys and the liver. under 18 years of age; thus, Evotaz should not be used in taking or thinking of taking, The brand name for atazanavir is Reyataz and it was pediatric patients. prescribed or not, as there originally boosted with ritonavir. are other drug interactions which are not listed here. ➤ SEE THE INDIVIDUAL should also be monitored. n MANUFACTURER n AVERAGE WHOLESALE PRICE DRUGS CONTAINED IN Kidney impairment, includ- n MORE INFORMATION Bristol-Myers Squibb $1,926.56/month EVOTAZ: Reyataz and ing cases of acute kidney Evotaz is an alternative evotaz.com Tybost. failure and Fanconi syn- PI for first-time therapy in (800) 321-1335 ➤ SEE PACKAGE INSERT for drome, has been reported DHHS HIV treatment guide- more complete informa- in patients taking both cobi- lines, and is one of two PIs tion on potential side cistat and Viread (tenofovir that are co-formulated with effects and interactions. DF or TDF, also found in the booster cobicistat (the Truvada). When used with other is Prezcobix). Since n POTENTIAL SIDE EFFECTS TDF, a baseline CrCl, urine most people who take AND TOXICITY glucose, and urine protein is Reyataz must use it with a The most common (greater needed; CrCl, urine glucose, PK enhancer like cobicistat than 10%) side effects and urine protein should be (Tybost) or ritonavir (Norvir), reported in clinical trials monitored regularly while this formulation makes were nausea, ocular icterus taking Tybost-containing for greater convenience, (yellowing of the eyes), and regimens. Observational one less pill, and one less jaundice. Rash has also cohort studies reported an co-pay. Tybost is not an been reported, though less association between some HIV medication. Similar to common. Cobicistat can PIs (including daruna- ritonavir, it is used to boost cause a small, reversible vir, found in Prezista and blood levels of other drugs. increase in serum creati- Prezcobix, and lopinavir/ The two PK enhancers have nine (SCr, which indicates ritonavir, brand name a long list of drug interac- the eGFR or estimated CrCl Kaletra) and an increased tions. Maintaining adequate lab values) within the first risk of cardiovascular (CV) hydration is important few weeks of treatment events; however, this has with Evotaz. Reyataz + without affecting actual kid- not been observed with Tybost + Epzicom is no ney function (see Tybost for Reyataz (atazanavir, or ATV), longer included in the list more information). Patients found in Evotaz. Another of “Recommended Initial experiencing a confirmed observational cohort study Regimens in Certain Clinical increase in serum creati- of predominantly male par- Situations” because it has nine of greater than 0.4 mg/ ticipants found a lower rate disadvantages when com- dL from baseline should be of cardiovascular events in pared with other regimens closely monitored for renal those receiving atazanavir- in this category. safety. Serum phosphorus containing regimens com- in patients with or at risk pared with other regimens. for kidney impairment Further study is needed. positivelyaware.com/evotaz POSITIVELY AWARE MARCH+APRIL 2019 45 2019 POSITIVELY AWARE HIV DRUG GUIDE

GENERIC IS AVAILABLE.

Reyataz atazanavir sulfate (atazanavir, or ATV) PI PROTEASE RECOMMENDED AS COMPONENT OF INHIBITOR ✔ INITIAL REGIMEN IN CERTAIN CLINICAL SITUATIONS

STANDARD DOSE • not take PPIs while on DR. DAVID HARDY SAYS: Approved in 2003, For most treatment-naïve (first time on HIV therapy) Reyataz. H2RAs like Pepcid Reyataz was the first effective and better-toler- and treatment-experienced individuals, the dose is one may be taken (no more than ated protease inhibitor alternative to the now forgot- 300 mg capsule plus 100 mg Norvir or 150 mg Tybost 20 mg twice a day if treat- ten Kaletra (a drug credited with saving many PLWH once daily with food. Must be taken in combination ment-experienced or 40 mg lives in the early 2000s, but loaded with significant with another antiretroviral(s) which does not contain twice a day if treatment- side effects). Reyataz can be given with or without a this drug or medication from the same drug class. naïve) at the same time as booster (Norvir or Tybost), but it is almost always See package insert for dosing recommendations during Reyataz/Norvir or at least given with a booster due to better resistance to HIV pregnancy, liver or kidney impairment, and with certain 10 hours later. When tak- resistance when taken that way. In a 3-way clinical drug interactions. Capsules also available in 150 mg ing Reyataz without Norvir, trial to find the best first-time ART regimen for PLWH, and 200 mg. Take Norvir or Tybost at same time as the dose can be taken at Reyataz + Norvir came in third after both Prezista + Reyataz. Pediatric dose with 50 mg oral powder avail- least two hours before or Norvir (second) and Isentress (first) due to its greater able based on body weight for children at least at least 10 hours after an side effects (nausea, queasiness, diarrhea, and yellow 3 months of age weighing at least 11 pounds (5 kg). H2RA. If taking chewable eyes and skin). Reyataz’s use has progressively fallen antacids like Rolaids and off over the past several years due to these study Take missed dose as soon as possible, unless it’s closer Tums, take Reyataz with results. Of note, Reyataz went off patent (marketing to the time of your next dose. Do not double up on your food two hours before or exclusivity) in the summer of 2017 and became avail- next dose. Swallow capsules whole—do not open or mix one hour after. Treatment- able as a generic form of the medication (atazanavir) with anything. Oral powder may be used by adult patients experienced people should in late December 2017. What effect this new generic, who cannot swallow the capsules. not take Reyataz with and most likely cheaper, version of Reyataz will have Sustiva. Viread decreases on its use will probably be minimal. the levels of Reyataz and ➤ SEE PACKAGE INSERT for between some PIs (DRV/r, Reyataz/Norvir increases ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: more complete informa- FPV, IDV, and LPV/r) and Viread levels; monitor for 0 Compared to previous PIs, Reyataz has a tion on potential side an increased risk of cardio- adverse events. Reyataz friendly lipid profile, eliminating any worries about effects and interactions. vascular events, while this can be taken unboosted metabolic complications. Drug interactions are a association was not noted with Epzicom if neces- concern. Acid reflux medications can interfere with n POTENTIAL SIDE EFFECTS with Reyataz. Another sary. Bepridil, amiodarone, the absorption of atazanavir. With atazanavir there is AND TOXICITY observational cohort study quinidine, and lidocaine an increase of bilirubin that, although not harmful, Most common side effects of predominantly male par- should be used cautiously causes yellowing of the eyes and skin. Watch the may include nausea, ocular ticipants found a lower rate because of the risk of kidneys and the liver. icterus (yellowing of the of cardiovascular events in worsening abnormal heart skin or eyes as a result of those receiving Reyataz- rhythm. Close monitor- increased bilirubin levels), containing regimens coming is required when used use lower dose of colchicine. Norvir + Epzicom is no jaundice, and rash. The pared with other regimens. with warfarin. Calcium Use with Norvir when tak- longer included in the list ocular icterus and jaundice Further study is needed. channel blockers should ing buprenorphine; monitor of “Recommended Initial was reversible on discon- With protease inhibitors, be monitored. Use caution for sedation. Do not take Regimens in Certain Clinical tinuation of the drug. Other there can be increased when using the antifungals with Zepatier. Taking with Situations” because it has less common side effects bleeding in hemophiliacs. itraconazole or ketocon- Olysio is not recommended. disadvantages when com- may include kidney stones, azole. Voriconazole is not Reyataz/Norvir is not rec- pared with other regimens gallstones, abnormal heart n POTENTIAL DRUG INTERACTIONS recommended. Reducing ommended with Harvoni in this category. rhythm, and elevated liver Do not use with alfuzosin, dose and frequency of if tenofovir DF (TDF, in enzymes (more common rifampin, irinotecan, ergot rifabutin to 150 mg every Truvada) is part of HIV regi- n MANUFACTURER in people with hepatitis derivatives, triazolam, oral other day or three times men. With Epclusa, moni- Bristol-Myers Squibb B or C). Capsules do not midazolam, St. John’s a week is recommended. tor for tenofovir toxicities if reyataz.com contain phenylalanine but wort, Revatio, or Viramune Reyataz + Norvir increases TDF is part of HIV regimen. (800) 321-1335 oral powder does; thus use (nevirapine). Do not use levels of fluticasone (found Take Reyataz with morning with caution in individuals lovastatin, simvastatin, or in Advair, Flonase, and Viekira Pak dose, without n AVERAGE WHOLESALE PRICE with phenylketonuria (PKU). co-formulations containing Flovent); monitor for signs Norvir. Tell your provider 300 mg, 30 capsules: Kidney laboratory testing them (Advicor and Vytorin) of Cushing’s syndrome. An or pharmacist about all $1,739.30/month should be performed in all for treatment of high cho- alternative corticosteroid is medications, herbals, and Generic atazanavir patients prior to initiation lesterol. Alternatives for recommended. Reyataz can supplements you are tak- 300 mg, 30 capsules: of Reyataz and continued these are atorvastatin, be taken with birth control ing or thinking of taking, $1,565.37/month during treatment. Renal rosuvastatin, pravastatin, pills that contain no more prescribed or not, as there laboratory testing should pitavastatin, and fluvas- than 30 mcg of ethinyl are many other drug interac- include serum creatinine, tatin, but should be used estradiol if taking Reyataz tions not listed here. estimated creatinine clear- with caution and started without Norvir and at least ance, and urinalysis with at the lowest dose pos- 35 mcg if taken with Norvir. n MORE INFORMATION microscopic examination. sible; monitor for increased Use caution with carbam- Yellowing of the eyes and Rarely, chronic kidney dis- side effects. Proton pump azepine, phenobarbital, and skin is a common reason ease has been observed. inhibitors (PPIs, like phenytoin. ED drugs should for discontinuation. Reyataz A cross-sectional cohort Aciphex, Dexilant, Nexium, not exceed 10 mg Cialis plus Norvir and 2 NRTIs is study reported Reyataz Protonix, and Prevacid) or 2.5 mg Levitra per 72 still recommended as a pre- with Norvir was associated and H2-receptor antago- hours, or 25 mg Viagra per ferred regimen during preg- with less progression to nists (H2RAs, like Pepcid, 48 hours. A lower dose of nancy. Reyataz plus Tybost atherosclerosis (a symptom Zantac, and Tagamet) can trazodone is recommended. is not recommended during of cardiovascular disease). stop Reyataz from being Use with caution with pregnancy. Maintaining ade- Large observational cohorts absorbed. Treatment- bosentan, salmeterol, and quate hydration is important found an association experienced people should immunosuppressants, and with Reyataz. Reyataz +

46 MARCH+APRIL 2019 POSITIVELY AWARE positivelyaware.com/reyataz 2019 POSITIVELY AWARE HIV DRUG GUIDE

GENERIC IS AVAILABLE.

Norvir ritonavir (RTV) PHARMACOKINETIC ENHANCER PKE (BOOSTER); ALSO AN ANTIRETROVIRAL USED ONLY ONLY AS A BOOSTER FOR OTHER DRUGS; RECOMMENDED (PROTEASE INHIBITOR) ✔ AS COMPONENT OF INITIAL REGIMEN IN CERTAIN CLINICAL SITUATIONS n STANDARD DOSE • Use calcium channel block- DR. DAVID HARDY SAYS: Norvir was the second Used as a boosting agent for other protease inhibitors ers (amlodipine, nifedipine, protease inhibitor approved to treat HIV, in (increases the levels of other PIs), at smaller doses of and others) with caution. early 1996. Over a short period of time its significant 100 to 200 mg, taken either once or twice a day with Norvir may alter warfarin side effects of nausea, vomiting, severe queasiness, the PI and a meal. levels; additional monitoring and explosive diarrhea (when taking 1,200 mg/day) is required. Norvir use with reduced its use as a protease inhibitor. By the late Take missed dose as soon as possible (at the same other blood thinners (antico- 1990s, it was used as the first booster (taking 100- time as the other PI prescribed) unless it’s closer to the agulants), such as Xarelto, 400 mg/day) for almost all other protease inhibitors time of your next dose. Do not double up on your next is not recommended. Norvir (except Viracept) and markedly increased the potency dose. Do not crush or chew tablets or capsules; always can increase anticoagulant and reduced the number of doses of protease inhibi- swallow whole. concentrations (and thereby tors. Even at lower doses, some PLWH have side Approved for children older than one month with increase risk of bleeding) or effects such as nausea, queasiness, and diarrhea. dosing based on body surface area; the use in children decrease their concentra- depends on the co-administered PI. Capsule formulation tions (and thereby decrease ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: requires refrigeration, but tablet does not. Liquid formula- effectiveness). Cialis, Levitra, 0 Once upon a time Norvir, or ritonavir, was tion available (80 mg/mL) in peppermint and caramel and Viagra levels are approved as a treatment for HIV. It was one of the first flavor, but is not very palatable. The taste of the liquid increased; doses should not PIs that slowed the death rates of HIV. For many, it can be improved by mixing with chocolate milk, peanut exceed 10 mg Cialis or 2.5 was the rescuer from certain death. As with the other butter, Ensure, or Advera within one hour of dosing. mg Levitra per 72 hours, or first generation PIs, it causes many debilitating side Liquid formula should not be taken by pregnant women, 25 mg Viagra per 48 hours. effects, including gastrointestinal problems and as it contains 43% alcohol. Norvir oral powder available Monitor for increased side increased risk for liver toxicity. Because of the way it in 100 mg packets, is free of alcohol and propylene glycol effects of these medications, is metabolized, ritonavir increases the blood level of (both of which are found in the liquid formula), and thus such as visual disturbances, other drugs. It was hard to take because of its toxici- safer for pediatric use. low blood pressure, dizzi- ties and drug interactions. Even though it failed as a ness, and prolonged painful treatment, it has proven to be, at a lower dose, an erection lasting longer than effective booster for newer and safer PIs. ➤ SEE PACKAGE INSERT for rifapentine, rifampin, vori- 4 hours. Effectiveness of more complete informa- conazole, ergot derivatives, oral contraceptives may be tion on potential side or the herb St. John’s wort. decreased; consider using n MORE INFORMATION with high-fat foods—how- effects and interactions. Do not use lovastatin or other or alternative methods The advantage of Norvir is ever, some other HIV medi- simvastatin or co-formula- of contraception. Levels of its use with other PIs as a cines should not be taken n POTENTIAL SIDE EFFECTS tions containing these drugs the street drug ecstasy are boosting agent (officially with high-fat foods. AND TOXICITY (Advicor and Vytorin) for the greatly increased by Norvir, in the drug class called The side effect potential treatment of high choles- and at least one death “pharmacokinetic enhanc- n MANUFACTURER of Norvir is much lower terol. Cholesterol-lowering has been attributed to the ers”). As such, it’s used to AbbVie now that it is only used alternatives are atorvastatin, combination. Using Norvir increase the levels of some norvir.com as a booster at low doses. rosuvastatin, pravastatin, with methamphetamines HIV protease inhibitor (PI) (800) 633-9110 Most common side effects pitavastatin, and fluvas- can result in up to 2–3 fold medications. An alterna- include stomach pain, nau- tatin, but should be used increase in methamphet- tive to Norvir was approved n AVERAGE WHOLESALE PRICE sea, diarrhea, and vomit- with caution and started at amine concentrations and in 2014 (see Tybost page). 100 mg, 30 tablets: ing. Other less common the lowest dose possible; puts user at risk for over- Stomach side effects are $308.60/month side effects may include monitor for increased side dose. GHB, another street reduced by taking Norvir generic $277.74 fatigue; tingling/numbness effects. Norvir increases drug, is also dangerous with around the mouth, hands, levels of nasal and inhaled Norvir. Clarithromycin levels or feet; loss of appetite; and fluticasone (found in can increase by up to 80%. taste disturbances. Norvir Advair, Flonase, Breo Co-administer bosentan, can also increase choles- Ellipta, Arnuity Ellipta, and salmeterol, and immuno- terol and triglyceride lev- Flovent), which may lead to suppressants with caution. els. Measure liver function Cushing’s syndrome. Use If co-administered, a lower before starting and then an alternative corticoste- dose of colchicine is rec- monitor, with perhaps clos- roid and monitor for signs ommended. Norvir, when er monitoring for those with of Cushing’s syndrome combined with another PI, underlying liver problems, (increased abdominal fat, may be taken with Sovaldi, especially during the first fatty hump between the Daklinza (dose may need several months. No dose shoulders, rounded face, adjustment), Epclusa (moni- adjustment necessary with red/purple stretch marks, tor for tenofovir toxicity mild to moderate liver dis- bone loss, possible high if TDF is part of regimen), ease, but Norvir is not rec- blood pressure, and some- and Harvoni (if TDF is not ommended for those with times diabetes). Trazodone part of HIV regimen). Norvir severe liver impairment. concentrations may + PI should not be taken increase; a lower dose of with Olysio, Viekira Pak, or n POTENTIAL DRUG INTERACTIONS trazodone is recommended. Zepatier. Tell your provider Norvir interacts with Norvir may decrease levels or pharmacist about all many drugs. Do not take of methadone, therefore medications, herbals, and with alfuzosin, amioda- titrate dose of methadone to supplements you are tak- rone, flecainide, lurasidone, clinical effect. Use caution ing or thinking of taking, propafenone, oral mid- with anticonvulsants such prescribed or not, as there azolam, triazolam, pimo- as carbamazepine, phe- are other drug interactions zide, ranolazine, Revatio, nobarbital, and phenytoin. which are not listed here. positivelyaware.com/norvir POSITIVELY AWARE MARCH+APRIL 2019 47 2019 POSITIVELY AWARE HIV DRUG GUIDE

Tybost cobicistat (COBI) PKE PHARMACOKINETIC ENHANCER USED ONLY AS A BOOSTER FOR OTHER DRUGS; RECOMMENDED (BOOSTER); NOT AN ANTIRETROVIRAL ✔ AS COMPONENT OF INITIAL REGIMEN IN CERTAIN CLINICAL SITUATIONS n STANDARD DOSE • may decrease Tybost drug DR. DAVID HARDY SAYS: Tybost was originally 150 mg once a day with food taken at the same levels. Do not take with developed as a booster for the integrase inhibi- time with either Prezista 800 mg (co-formulated as Olysio, Viekira Pak, or tor elvitegravir (see Stribild and Genvoya). In a head- Prezcobix), Reyataz 300 mg (co-formulated as Evotaz), Zepatier. Avoid Harvoni if to-head comparison of Reyataz (plus 2 NRTIs) or co-formulated in the single-tablet regimens Stribild tenofovir disoproxil fuma- boosted with Tybost or Norvir, no significant differ- and Genvoya. rate (TDF) is part of the ences in effectiveness or side effects between the HIV regimen. Tybost has two boosters was seen. In fact, on a molecular basis, Tybost is not an HIV drug; it is a pharmacokinetic similar drug interactions the two drugs are almost identical. A few small enhancer or a “booster” used to increase the levels of as Norvir, but they are not molecular changes in Tybost have taken away its anti- Prezista 800 mg once daily, Reyataz 300 mg once daily, interchangeable and there HIV activity, so it is not considered an antiretroviral, or elvitegravir 150 mg in Stribild and Genvoya. Tybost is may be some drug interac- unlike Norvir. Tybost has fewer unwanted drug-drug not interchangeable with Norvir when used to increase tions with Tybost that are interactions compared to Norvir. the levels of other HIV medications. not observed with Norvir. Take missed dose as soon as possible (at the same Tybost may increase levels ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: time as any separate medication prescribed) unless it’s of methamphetamines. Tell 0 Tybost, or cobicistat, is a drug developed to closer to the time of your next dose. Tybost is not recom- your provider or pharma- work as an enhancer to boost the level of other HIV mended for people with CrCl less than 70 mL/min when cist about all medications, drugs. Cobicistat is not an antiviral. This enhancer co-administered with a regimen containing TDF or for herbals, and supplements inhibits a liver enzyme used by many HIV drugs to be people with severe liver problems. you are taking or thinking metabolized in the liver. Being a CYP3A4 inhibitor like of taking, prescribed or ritonavir, it might cause the same side effects as rito- not, as there are other drug navir: increased triglycerides and cholesterol, as well ➤ SEE PACKAGE INSERT for irinotecan, simvastatin, interactions which are not as drug-drug interaction with many other drugs. One more complete informa- lovastatin, lurasidone, listed here. good thing about cobicistat is that it is less expensive tion on potential side methyl-ergonovine, rano- and licensed for use in fixed-dose combinations. effects and interactions. lazine, rifampin, pimozide, n MORE INFORMATION triazolam, oral midazolam, Tybost is not an HIV medi- n POTENTIAL SIDE EFFECTS Revatio, or St. John’s wort. cation. It is used to boost n MANUFACTURER n AVERAGE WHOLESALE PRICE AND TOXICITY Tybost may increase levels blood levels of Prezista Gilead Sciences, Inc. $263.87/month Side effects observed in of nasal or inhaled flutica- and Reyataz and is avail- gilead.com clinical studies (greater than sone (Flonase, Advair, Breo able in fixed-dose tablets tybost.com 2% of patients) include nau- Ellipta, Arnuity Ellipta, and with those medications (800) GILEAD-5 sea, jaundice, and yellowing Flovent). Use an alternative (see Evotaz and Prezcobix). (445–3235) of the eyes. However, it was corticosteroid and monitor Cobicistat is also part of studied with Reyataz so the for signs of Cushing’s syn- the single-tablet regimens jaundice and yellowing of drome (increased abdomi- Genvoya and Stribild, both eyes were most likely due nal fat, fatty hump between recommended therapies to the Reyataz component. the shoulders, rounded in the DHHS treatment Before taking Tybost, kid- face, red/purple stretch guidelines in certain ney function testing should marks, bone loss, possible clinical situations. Tybost be conducted, including high blood pressure, and shares some of the same serum creatinine, serum sometimes diabetes). No side effects of increased phosphorus, urine glucose, significant interactions with cholesterol and increased and urine protein. These beclomethasone. Tybost triglycerides as Norvir; measurements should con- may increase levels of however in clinical trials tinue to be monitored while certain calcium channel they were less pronounced. taking Tybost. Cobicistat blockers, beta blockers, Tybost co-administered can cause a small, revers- HMG-CoA reductase inhibi- with darunavir or atazana- ible increase in serum cre- tors (statins or cholesterol vir should not be initiated atinine within the first few medicines), anticoagulants, in pregnant individuals and weeks of treatment without antiplatelets, antiarrhyth- is not recommended dur- affecting actual kidney mics, antidepressants, ing pregnancy. Inadequate function. The SCr increase sedative-hypnotics, rifabu- levels of ART in second and occurred within weeks of tin, bosentan, erectile dys- third trimesters as well as starting cobicistat and was function agents, inhaled viral breakthroughs have reversible within a few days corticosteroids, and norg- been reported. Tybost is not after stopping it. The co- estimate. Caution should recommended during preg- adminstration of Tybost and be taken, with possible nancy. Tybost has not been Viread (tenofovir DF or TDF, dose adjustments of these studied separately from also found in Complera, medications, when used Genvoya, Stribild, Symtuza, Stribild, and Truvada) is not with Tybost. Sporonox Prezcobix, or Evotaz in indi- recommended if the CrCl is (antifungal) and Biaxin (anti- viduals under 18 years of less than 70 mL/min. biotic) may increase Tybost age; thus Tybost should not concentrations. Tybost be used in pediatric patients. n POTENTIAL DRUG INTERACTIONS may also increase Biaxin Tybost interacts with levels. Rifabutin and some many drugs. Do not take anti-seizure medications, with alfuzosin, colchi- such as carbamazepine cine, dihydroergotamine, (Tegretol), phenobarbital, dronedarone, ergotamine, and phenytoin (Dilantin)

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Descovy emtricitabine/tenofovir alafenamide (FTC/TAF) FIXED-DOSE COMBINATION OF NRTI TWO NUCLEOSIDE REVERSE TRANSCRIPTASE RECOMMENDED AS COMPONENT INHIBITORS (NUCLEOSIDE, OR “NUKE”) ★ OF INITIAL REGIMEN FOR MOST PEOPLE n STANDARD DOSE • kidneys, including chronic DR. DAVID HARDY SAYS: Descovy was approved One tablet once daily, without regard to food. Tablet use or high doses of anti- in mid-2016 as the “new and improved” version contains 200 mg emtricitabine and 25 mg tenofovir inflammatory drugs for of Truvada as it maintained the Emtriva (FTC) and alafenamide. Must be taken in combination with pain like Advil or Motrin changed the Viread (tenofovir DF) to TAF. This change another antiretroviral(s) which does not contain the (ibuprofen) and Aleve was prompted by the finding that TAF (originally medications in this drug or medication from the same (naproxen). Descovy should discovered and developed in 2002, but then shelved drug class. not be taken with certain for several years) produced similar HIV-suppressing anticonvulsants (including effects as Viread with much lower levels of the same For adults and children weighing at least 55 pounds carbamazepine, oxcarbaze- drug in the blood. The lower tenofovir levels have (25 kg). Crushing or splitting tablets has not been studied pine, phenobarbital, and been shown to have less harmful effects on the and is not recommended; TAF is soluble in water, but has phenytoin), Aptivus/Norvir, kidneys and bone mineral density (bone strength). a bitter and burnt aromatic flavor profile. rifabutin, rifampin, rifa- Descovy is the most preferred two-nuke combination Take a missed dose as soon as possible, unless it is pentine, or St. John’s wort. used by HIV treaters when building first-time ART closer to the time of your next dose. Do not double up Can be used with hepatitis regimens for their PLWH. on your next dose. Descovy should not be used if CrCl is C drugs such as Epclusa, less than 30 mL/min or if you are on dialysis. In children Harvoni, Sovaldi, Olysio, ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: weighing 55 to 77 pounds (25 – 35 kg), taking Descovy Daklinza, Viekira Pak, or 0 Descovy is the new Truvada, in the sense that with a boosted HIV protease inhibitor medication is not Zepatier. Tell your provider it contains emtricitabine plus tenofovir alafenamide recommended. Unlike Truvada, Descovy is not approved or pharmacist about all instead of the original tenofovir disoproxil fumarate. for and should not be used for prevention of HIV (pre- medications, herbals, and What is better about combining with TAF is that TAF exposure prophylaxis, or PrEP). supplements you are tak- has fewer kidney and bone density problems. ing or thinking of taking, Descovy has not been approved for PrEP, however. prescribed or not, as there It is to be used to treat HIV in combination with other ➤ SEE THE INDIVIDUAL with or without muscular are other drug interactions antivirals prescribed by your doctor. Many new STRs DRUGS CONTAINED IN pain or weakness, as well which are not listed here. contain TAF already. Drug interactions may occur, DESCOVY: Emtriva (but as any concerning changes so discuss with your doctor all medications taken, TAF is not available in urinary habits, as these n MORE INFORMATION including over-the-counter medicines. A Phase 3, separately for HIV). could be signs of kidney Descovy is the newer ver- randomized, double-blind trial named Discover ➤ SEE PACKAGE INSERT for problems. If you have HIV sion of Truvada. Instead is under way, comparing Descovy and Truvada’s more complete informa- and HBV, guidelines rec- of TDF, Descovy contains efficacy in preventing HIV. tion on potential side ommend treatment for both TAF (tenofovir alafenamide), effects and interactions. viruses. Descovy can be which reduces serum teno- used to treat HIV and HBV fovir concentration by 90%. However, unlike Truvada, routine use of Descovy in n POTENTIAL SIDE EFFECTS simultaneously. If you are This results in lessened Descovy is not approved for pregnant women at this AND TOXICITY co-infected with HBV and impact on kidney and bone and should not be used for time. Descovy tablets are Overall, Descovy is well HIV, you should not stop mineralization but main- PrEP. A clinical trial called relatively small compared tolerated, but some may Descovy without medical tains potent antiviral activity DISCOVER is currently to Truvada and other com- experience nausea, head- supervision because it can inside the CD4 cell. In clini- in progress comparing bination tablets, which ache, stomach pain, or cause your HBV to flare cal trials, fewer kidney and Descovy to Truvada for PrEP may be an advantage for weight loss. Rare skin and cause you to experi- bone issues were observed (prevention) in HIV-negative patients who have difficulty discoloration on palms ence signs and symptoms with TAF than with TDF, individuals. Because both swallowing. and soles may also occur. of acute hepatitis. HBV and significant improve- FTC and TAF are also active May affect the bones and should be closely moni- ments were seen when against hepatitis B (HBV), n MANUFACTURER kidneys. In clinical trials, tored by your provider. switching from TDF to TAF. Descovy is recommended Gilead Sciences, Inc. fewer bone and kidney The long-term impact of TAF by DHHS for individuals gilead.com issues were observed n POTENTIAL DRUG INTERACTIONS on patients with osteopenia co-infected with both HIV descovy.com with the TAF formulation Do not take with Epivir- or osteoporosis is unknown. and hepatitis B. Pediatric (800) GILEAD-5 compared to the TDF for- HBV, Hepsera, or Vemlidy Both Descovy and Truvada HIV guidelines list Descovy (445–3235) mulation. Tell your provider (TAF), used for the treat- are currently recommended as part of a preferred regi- about any pain in extremi- ment of hepatitis B. Use by DHHS HIV treatment men. There is insufficient n AVERAGE WHOLESALE PRICE ties, persistent or worsen- caution with drugs that guidelines for first-time data in pregnancy for the $2,010.95/month ing bone pain and fractures, negatively affect the therapy for most people. DHHS to recommend the

positivelyaware.com/descovy POSITIVELY AWARE MARCH+APRIL 2019 49 2019 POSITIVELY AWARE HIV DRUG GUIDE

APPROVED AS GENERIC, WHICH IS NOT YET COMMERCIALLY AVAILABLE.

Truvada emtricitabine/tenofovir DF (FTC/TDF) FIXED-DOSE COMBINATION OF NRTI TWO NUCLEOSIDE REVERSE TRANSCRIPTASE RECOMMENDED AS COMPONENT INHIBITORS (NUCLEOSIDE, OR “NUKE”) ★ OF INITIAL REGIMEN FOR MOST PEOPLE n STANDARD DOSE • is taken with Truvada or DR. DAVID HARDY SAYS: Truvada was approved One tablet once daily without regard to food for adults Viread, it is recommended in 2004 (on the same day as Epzicom, see that and children weighing at least 77 pounds. In children that Reyataz 300 mg is page) as a two-drugs-in-one-pill, two-nuke combina- weighing 37–76 pounds, Truvada is dosed based on taken with Norvir 100 mg tion “backbone” to which a third drug is added to cre- body weight. See package insert for weight-based or Tybost 150 mg (all as ate a three-drug combination or “cocktail” ART dosing. Truvada tablets are available in the follow- a single daily dose with regimen. Truvada was the most commonly prescribed ing emtricitabine/tenofovir DF dosages: 100/150 mg food). In addition, Reyataz/ antiretroviral for the majority of PLWH from the late tablets, 133/200 mg tablets, 167/250 mg tablets, and Norvir, Prezista/Norvir, and 2000s until Descovy was approved in 2016. This was 200/300 mg tablets. Tablets can disintegrate in water, Kaletra increase tenofovir due to Truvada’s solid track record as a potent, well- grape juice, or orange juice with minor stirring and concentrations. It is recom- tolerated, and durable two-nuke combination, data pressure from a spoon; however, no studies have been mended that patients taking showing its higher potency over Epzicom, and con- performed to evaluate the pharmacokinetics (PK) or Reyataz/Norvir, Prezista/ cerns (still controversial) about Epzicom’s cardiovas- stability of crushed vs. intact tablets. Must be taken in Norvir, or Kaletra with cular side effects. Truvada’s use has steadily declined combination with another antiretroviral(s) which does Truvada should be moni- since the approval of three TAF-containing medica- not contain the medications in this drug or medication tored for Truvada-associated tions (Genvoya, Odefsey, and Descovy) due to less from the same drug class. adverse events, particularly long-term side effects (kidney and bone strength). decreases in kidney func- Truvada became the first, and still only, medication Take a missed dose as soon as possible, unless it is tion. Avoid taking Truvada approved for pre-exposure prevention (PrEP) of HIV, closer to the time of your next dose. Do not double up with drugs that negatively in 2012. In mid-December 2017, a generic form of on your next dose. The dosing frequency needs to be affect the kidneys, includ- Truvada was approved in the U.S. With the availability adjusted for people with decreased kidney function. The ing chronic use or high of TAF-containing medications, the use of generic dose of Truvada should be adjusted if CrCl is less than doses of anti-inflammatory Truvada, while probably less expensive, has yet to 50 mL/min and Truvada should not be used if CrCl is less drugs for pain like Advil be seen. than 30mL/min or if you are on dialysis. or Motrin (ibuprofen) and Aleve (naproxen). Truvada ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: may be used with hepatitis 0 Truvada is the brand name of a fixed-dose com- ➤ SEE THE INDIVIDUAL be signs of kidney problems. C drugs such as Daklinza, bination containing emtricitabine and tenofovir diso- DRUGS CONTAINED IN Routine monitoring of esti- Harvoni, Olysio, Sovaldi, proxil fumarate. Both drugs have a long half-life and TRUVADA: Viread and mated creatinine clearance, Viekira Pak, or Zepatier, when combined can be taken once a day. Truvada is Emtriva. serum phosphorus, urine depending on the third drug the most prescribed NRTI fixed-dose combination glucose, and urine protein in the HIV regimen. Monitor with other antiretrovirals. It may cause damage to the ➤ SEE PACKAGE INSERT for should be performed in for tenofovir toxicities if kidneys and loss of bone density. It is important to more complete informa- all individuals with mild used with Epclusa. Tell monitor kidney function and bone density. Besides tion on potential side kidney impairment. If you your provider or pharma- that, it is well tolerated and potent. effects and interactions. have HIV and HBV, guide- cist about all medications, lines recommend treatment herbals, and supplements n POTENTIAL DRUG INTERACTIONS for both viruses. Truvada you are taking or thinking of baseline viral load. Kidney n MANUFACTURER Overall, it is well tolerated, can be used to treat HIV taking, prescribed or not, as function must be monitored Gilead Sciences, Inc. but some may experience and HBV simultaneously. there are other drug inerac- before and during treat- gilead.com nausea, headache, gas, If you are co-infected with tions not listed here. ment with Truvada and it truvada.com stomach pain, or weight HBV and HIV, you should may not be a good option (800) GILEAD-5 loss. Rare skin discolor- not stop Truvada with- n MORE INFORMATION for patients with underly- (445–3235) ation on palms and soles out medical supervision Current DHHS HIV treating kidney problems. Fewer may also occur. The TDF because it can cause your ment guidelines recom- kidney and bone issues n AVERAGE WHOLESALE PRICE in Truvada is associated HBV to flare and cause mend Truvada (or Descovy) were seen with the TAF for- $2,010.95/month; with long-term decreases you to experience signs over Epzicom as the pre- mulation compared to TDF Approved as generic; not in bone mineral density and symptoms of acute ferred NRTI component in clinical trials. Approved yet commercially available (BMD). BMD monitoring hepatitis. HBV should be for initial therapy (unless in 2012 for HIV prevention should be considered in closely monitored by your Epzicom is paired with (pre-exposure prophylaxis, people who have a his- provider. Truvada is associ- Tivicay). The newer version or PrEP) in confirmed HIV- tory of bone fracture due ated with lower lipid levels of Truvada, called Descovy, negative adults; see Truvada to disease or are at risk for than Ziagen or tenofovir AF was approved in 2016. The for PrEP page. Truvada is osteopenia or osteoporosis. (TAF) due to tenofovir DF’s ACTG A5202 study report- recommended by DHHS While calcium and vitamin favorable effect on cho- ed that while both Epzicom as one of the preferred D levels can be checked to lesterol. Truvada contains and Truvada reduced viral NRTI combination compo- assess the need for these lactose, which can cause load, for those people who nents of an ART regimen in supplements, talk with some abdominal discom- started treatment with a pregnancy. your provider before start- fort, especially in patients viral load of more than ing on your own. Truvada sensitive to lactose. 100,000 copies/mL, the can cause kidney toxicities. times to virologic failure and Tell your provider about any n POTENTIAL DRUG INTERACTIONS the first adverse event were pain in extremities, per- Do not take with Epivir- both significantly shorter sistent or worsening bone HBV, Hepsera, or Vemlidy in patients taking Epzicom pain and fractures, with or (TAF), used for the treat- compared to Truvada. In without muscular pain or ment of hepatitis B. studies using Tivicay in the weakness, as well as any Tenofovir decreases the con- regimen, however, Truvada concerning changes in uri- centration levels of Reyataz, and Epzicom were equally nary habits, as these could therefore when Reyataz effective regardless of

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Cimduo lamivudine/tenofovir DF (3TC/TDF) FIXED-DOSE COMBINATION OF TWO NUCLEOSIDE NRTI REVERSE TRANSCRIPTASE INHIBITORS RECOMMENDED FOR INITIAL ART FOR MOST PERSONS (NUCLEOSIDE, OR “NUKE”) ★ WHEN COMBINED WITH TIVICAY OR ISENTRESS n STANDARD DOSE • decompensation, some DR. DAVID HARDY SAYS: Cimduo became the One tablet once daily without regard to food for adults fatal, has occurred when second generic two-nucleoside fixed-dose- and children weighing at least 77 pounds (35 kg). Tablet using lamivudine and inter- combination tablet when it was approved by the FDA contains 300 mg lamivudine (3TC) and 300 mg tenofovir feron alfa (with or without in March 2018 (see Epzicom). Like the FDA approval disoproxil fumarate (TDF). Must be taken in combination ribavirin) for hep C treat- of Symfi and Symfi Lo (also manufactured by Mylan; with another antiretroviral(s) which does not contain the ment. (Of note, interferon see that page), Cimduo was approved based upon medications in this drug from the same drug class. alfa is no longer used for pharmacokinetic bioequivalence data, not clinical the treatment of hepatitis trial data, as the two agents in it, tenofovir DF and Take a missed dose as soon as possible, unless it is C). Cimduo and Temixys lamivudine, were already approved as antiretroviral closer to the time of your next dose. Do not double up on may be used with hepatitis medications (see Symfi/Symfi Lo). Similar to Symfi your next dose. C drugs such as Daklinza, and Symfi Lo, Cimduo is not an exact generic version The dosing frequency needs to be adjusted for people Harvoni, Olysio, Sovaldi, of Truvada, as lamivudine is used in place of Emtriva with decreased kidney function. Cimduo and Temixys Viekira Pak, or Zepatier, (emtricitabine), but even the FDA accepted clinical should not be used if CrCl is less than 50 mL/min or if depending on the third drug data from trials using tenofovir DF plus lamivudine in you are on dialysis. in the HIV regimen. Monitor their original review and approval of Truvada, so the for tenofovir toxicities if difference between Cimduo and Truvada is minimal used with Epclusa. Avoid and not clinically important. Comparing the cost of ➤ SEE THE INDIVIDUAL impairment. If you have use of sorbitol-containing Cimduo: the wholesale acquisition cost (WAC) for a DRUGS CONTAINED IN HIV and HBV, guidelines medicines with lamivudine. 30-day supply is $1,005, compared to $1,676 for both CIMDUO AND TEMIXYS: recommend treatment for Tell your provider or pharma- Truvada and Descovy, $1,292 for Ziagen, and $185– Epivir and Viread. both viruses. Cimduo can cist about all medications, $1,116 for generic abacavir/lamivudine. ➤ SEE PACKAGE INSERT for be used to treat HIV and herbals, and supplements more complete informa- HBV simultaneously. If you you are taking or thinking of ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: tion on potential side are co-infected with HBV taking, prescribed or not, as 0 Cimduo is a fixed-dose combination containing effects and interactions. and HIV, you should not there are other drug interac- lamivudine and tenofovir DF, and is to be used in com- stop Cimduo without medi- tions not listed here. bination with other antiretrovirals. It has proven to be n POTENTIAL SIDE EFFECTS cal supervision because it highly effective and relatively safe. The most com- AND TOXICITY can cause your HBV to flare n MORE INFORMATION mon adverse effects are associated with tenofovir Most common adverse and cause you to experi- This slightly different DF: potential kidney damage and bone density loss. events (in more than 10% ence signs and symptoms version of Truvada was Similar to other HIV drugs, it is important to monitor of people taking it) are of acute hepatitis. HBV FDA approved last year. It liver functions. Cimduo was developed by Mylan. headache (14%), pain should be closely monitored contains 3TC instead of (13%), depression (11%), by your provider. Cimduo Truvada’s FTC. The three diarrhea (11%), and rash contains lactose, which meds are essentially equiva- for patients with underly- historical data noted viral (18%) (when studied in can cause some abdominal lent. The niche for Cimduo ing kidney problems. When resistance was more com- combination with efavirenz). discomfort, especially in is that it may be a cheaper the virologic efficacy of mon with Cimduo than with Rare skin discoloration on patients sensitive to lactose. option for some insurance Cimduo was compared to Truvada, however this was palms and soles may also plans because it contains Truvada (each combined not observed in clinical occur. The TDF in Cimduo n POTENTIAL DRUG INTERACTIONS generic drugs. It also allows with Sustiva or nevirapine trials. Cimduo is recom- is associated with long-term Do not take with Epivir-HBV, for some new or unique co- or a boosted PI) in a study, mended by DHHS as one decreases in bone mineral Hepsera, or Vemlidy (TAF), formulations (such as with Cimduo was associated of the preferred NRTI com- density (BMD). BMD moni- used for the treatment Delstrigo, Symfi, and Symfi with higher rates of viro- bination components of an toring should be considered of hepatitis B. Tenofovir Lo). Cimduo has received logic failure compared to ART regimen in pregnancy. in people who have a his- decreases the concentration DHHS HIV treatment Truvada when paired with Another drug containing tory of bone fracture due levels of Reyataz, therefore guidelines recommendation an NNRTI; however, there the same medications as to disease or are at risk for when Reyataz is taken with as a component for initial was no difference in the Cimduo, Temixys, was FDA osteopenia or osteoporosis. Cimduo or Temixys, it is ART in most people with rates of virologic failure approved but is not com- While calcium and vitamin recommended that Reyataz HIV when combined with when paired with a boosted mercially available. D levels can be checked to 300 mg is taken with Norvir dolutegravir or raltegravir. PI. It should be noted that assess the need for these 100 mg (all as a single daily TDF is falling out of favor the people in the study n MANUFACTURER supplements, talk with your dose with food). In addition, since the newer formulation who were taking Cimduo Mylan Specialty L.P. provider before starting on Reyataz/Norvir, Prezista/ tenofovir alafenamide, or generally had higher viral mylan.com your own. TDF can cause Norvir, and Kaletra increase TAF, was approved. TAF is loads, lower CD4 counts, cimduo.com kidney toxicities. Tell your tenofovir concentrations; safer on kidneys and bones and were more likely to be (877) 446-3679 provider about any pain in therefore, it is recommend- than TDF. Unlike Truvada, using injection drugs at the extremities, persistent or ed patients be monitored Cimduo is not approved start of the study compared n AVERAGE WHOLESALE PRICE worsening bone pain and for TDF-associated adverse for PrEP (HIV prevention). to patients taking Truvada. $1,206.56/month fractures, with or without events, particularly decreas- DHHS treatment guide- Another study examining muscular pain or weakness, es in kidney function. Avoid lines recommend Cimduo, as well as any concerning taking Cimduo with drugs Truvada, or Descovy (which changes in urinary habits, that negatively affect the contains TAF) over Epzicom as these could be signs of kidneys, including chronic as the preferred NRTI com- kidney problems. Routine use or high doses of anti- ponent for initial therapy monitoring of estimated inflammatory drugs for pain (unless Epzicom is paired creatinine clearance, serum like Advil or Motrin (ibupro- with Tivicay). Kidney func- phosphorus, urine glucose, fen) and Aleve (naproxen). tion must be monitored and urine protein should Avoid administration of before and during treat- be performed in all indi- sorbitol with Cimduo and ment with Cimduo and it viduals with mild kidney Temixys. Hepatic (liver) may not be a good option positivelyaware.com/cimduo POSITIVELY AWARE MARCH+APRIL 2019 51 2019 POSITIVELY AWARE HIV DRUG GUIDE

GENERIC IS AVAILABLE.

Epzicom abacavir/lamivudine (ABC/3TC) FIXED-DOSE COMBINATION OF TWO NUCLEOSIDE RECOMMENDED AS COMPONENT OF INITIAL REGIMEN NRTI REVERSE TRANSCRIPTASE INHIBITORS FOR MOST PEOPLE WHEN USED IN COMBINATION WITH (NUCLEOSIDE, OR “NUKE”) ★ DOLUTEGRAVIR (AS TRIUMEQ) n STANDARD DOSE • because it can cause your DR. DAVID HARDY SAYS: Approved on the same One tablet once daily, without regard to food. Tablet HBV to flare up and cause day in 2004 as Truvada, Epzicom is also a two- contains 600 mg abacavir and 300 mg lamivudine. you to experience signs and drugs-in-one-pill, two-nuke combination “backbone” Must be taken in combination with another antiretroviral(s) symptoms of acute hepati- to which a third drug is added to build a three-drug which does not contain the medications in this drug or tis. HBV should be closely combination or “cocktail” ART regimen (just like medication from the same drug class. monitored by your provider. Truvada). Because Epzicom contains Ziagen (abacavir), a one-time blood or mouth swab test must be Take missed dose as soon as possible, unless it is n POTENTIAL DRUG INTERACTIONS done to look for a genetic marker (HLA-B*5701) closer to the time of your next dose. Do not double up on Do not take with Epivir- which predicts a severe allergic reaction to Ziagen if your next dose. Approved for adults and children weighing HBV, used for the treat- present. In 2008, a European cohort study raised con- 55 pounds (25 kg) or more. Not recommended for those ment of hepatitis B. Alcohol cern about an association of Ziagen with the with decreased kidney function (creatinine clearance less can increase the levels of increased occurrence of heart attacks. Although than 50 mL/min) due to lamivudine component, or those abacavir and therefore can many other studies have weighed in, trying to con- with mild liver impairment due to abacavir component. increase the possibility of firm or refute this finding, there still remains contro- Alternative doses may be obtained by using the individual side effects. Epzicom may versy whether cardiovascular disease (heart attacks) components of this medication. be used with hepatitis C is a true side effect of Ziagen or a false association. drugs such as Daklinza, Not long after this, a large clinical trial comparing Epclusa, Harvoni, Olysio, first-time ART regimens for PLWH with either ➤ SEE THE INDIVIDUAL find out if you should stop Sovaldi, Viekira Pak, or Epzicom or Truvada found that Epzicom was not as DRUGS CONTAINED IN taking Epzicom. If you stop Zepatier, depending on the potent for PLWH with high viral loads (greater than EPZICOM: Epivir and Epzicom because of an third drug in the HIV regi- 100,000 copies/mL). These two findings diminished Ziagen. allergic reaction, never take men. There have been rare the use of Epzicom and Ziagen in favor of Truvada. A ➤ SEE PACKAGE INSERT for Epzicom or an abacavir- reports of depression and generic version of Epzicom has been available in the more complete informa- containing regimen such as suicidal ideation, primarily U.S. since September 2016. Today most Epzicom use tion on potential side Triumeq, Trizivir, or Ziagen in patients with a history is prescribed as two of the three medications in the effects and interactions. again (called “rechalleng- of psychiatric illnesses, in STR Triumeq (Tivicay/Ziagen/Epivir). ing”). Rechallenging could people receiving INSTI- n POTENTIAL SIDE EFFECTS cause a rare life-threatening based regimens. Avoid use ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: AND TOXICITY reaction. This does not of sorbitol-containing medi- 0 Epzicom is a fixed-dose combination tablet The length of this section apply to a missed dose cines with lamivudine; there containing abacavir and lamivudine. Epzicom is used is meant to be informa- when HSR is not suspected, are many, such as acet- as an alternative to Truvada in patients who can’t tive, not scary. Common but talk with your health- aminophen liquid (Tylenol tolerate tenofovir due to kidney toxicity or loss of side effects may include care provider and watch for liquid and others). Tell bone density. Epzicom may increase the risk of heart headache, nausea, fatigue, symptoms if you’ve stopped your provider or pharma- attacks and cardiovascular disease due to abacavir. depressed mood, dizziness, the drug for at least a few cist about all medications, It is not as effective in patients whose viral load is diarrhea, and insomnia. Of days. herbals, and supplements more than 100,00 copies. It is combined with note is the hypersensitivity Some large observational you are taking or thinking of dolutegravir in the fixed-dose tablet branded as reaction (HSR, an allergic- studies suggest abacavir taking, prescribed or not, as Triumeq. Epzicom is recommended as first-line like reaction) warning on may increase the risk of car- there are other drug interac- treatment in combination with dolutegravir. abacavir (see Ziagen for diovascular events, includ- tions not listed here. details of symptoms). To ing myocardial infarction minimize the risk for HSR, a (MI, or heart attack), in peo- n MORE INFORMATION Epzicom performed just as n MANUFACTURER blood test for HLA-B*5701 ple with greater risk factors Triumeq, a single-tablet well as Truvada in people ViiV Healthcare (a genetic marker) should be such as smoking, diabetes, regimen (STR) containing with high viral loads (over viivhealthcare.com done prior to starting an HIV high blood pressure, older Tivicay and Epzicom, is a 100,000 copies/mL). (877) 844-8872 regimen containing Epzicom age, high cholesterol, fam- DHHS recommended ini- Hence, Triumeq is the epzicom.com to identify patients at higher ily history of heart disease, tial therapy in most people only abacavir-containing risk for this reaction. A nega- and drug use. Other stud- (again, test for HLA-B*5701 regimen recommended by n AVERAGE WHOLESALE PRICE tive HLA-B*5701 test does ies have found no increased first). Otherwise, the guide- DHHS as initial therapy for $1,550.05/month; not mean you won’t have risk. To date, no consensus lines recommend Descovy most HLA-B*5701 negative generic: $1,395.05/month HSR, but the risk is reduced has been reached on the or Truvada over Epzicom people. The lamivudine por- to 1% from clinical stud- association of abacavir with as the backbone NRTI tion of Epzicom is also used ies. This test is covered by cardiac risk or a possible component of an HIV drug to treat the hepatitis B virus most insurance and also by mechanism for the associa- combination for first-time (HBV); see Epivir. Epzicom LabCorp/ViiV (see company tion. People who have high therapy, with Epzicom is recommended by DHHS contact on co-pay chart). risk for heart disease should listed as an alternative as one of the preferred An HSR can technically discuss risks with their pro- NRTI backbone. One of the NRTI combination compo- occur at any time, regard- vider, and they should be reasons abacavir is a DHHS nents of an ART regimen in less of how long you have monitored more closely. If alternative drug is that the pregnancy. taken the medication, how- you have HIV and HBV, ACTG A5202 study found ever, it is much more likely guidelines recommend that abacavir/lamivudine to occur when you start treatment for both viruses. (Epzicom) was inferior to (or re-start) the medica- The lamivudine component tenofovir/emtricitabine tion (90% occur within the of Epzicom can be used to (Truvada) in getting people first 6 weeks of treatment). treat HIV and HBV simulta- undetectable when their Symptoms of an HSR usual- neously. If you are co-infect- pre-treatment viral load was ly worsen, very slowly, with ed with HBV and HIV, you over 100,000 copies/mL. every dose. Call your health- should not stop Epzicom However, when combined care provider right away to without medical supervision with Tivicay (dolutegravir),

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Emtriva emtricitabine (FTC) NRTI NUCLEOSIDE REVERSE TRANSCRIPTASE RECOMMENDED AS COMPONENT INHIBITOR (NUCLEOSIDE, OR “NUKE”) ★ OF INITIAL REGIMEN FOR MOST PEOPLE n STANDARD DOSE • used with hepatitis C drugs DR. DAVID HARDY SAYS: Emtriva was approved One 200 mg capsule once daily without regard to food. such as Daklinza, Epclusa, in 2003 and has been a closely related medica- Dosing needs to be adjusted for adults and children Harvoni, Olysio, Sovaldi, tion to Epivir (lamivudine or 3TC). Note the similar who have decreased kidney function (creatinine Viekira Pak, or Zepatier, chemical names FTC and 3TC. For many HIV treaters, clearance less than 50 mL/min). See package insert depending on the other ART guidelines writers, and even the FDA, the two for guidance on dosing in the setting of kidney impair- components in the HIV medications are interchangeable. Emtriva is almost ment. Must be taken in combination with another regimen. always used in combination with Viread (Truvada) or antiretroviral(s) which does not contain the medication with TAF (Descovy). It is a potent antiretroviral, but its in this drug. n MORE INFORMATION anti-HIV activity is almost completely lost when a Emtriva (emtricitabine) is very common, single mutation (M184V) occurs in the Indicated for adults and children regardless of age. similar to Epivir (lamivu- virus. It has very few, if any, significant side effects Emtriva is dosed based on body weight for children. See dine): both treat HIV and and therefore is almost always included in most ART the package insert for weight-based dosing. HBV and have the same regimens. Take missed dose as soon as possible, unless it is resistance profile, meaning closer to the time of your next dose. Do not double up that if your virus is resis- ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: on your next dose. It is also available as an oral solution tant to one drug, it will be 0 Emtriva or emtricitabine is a very safe and well- (10 mg/mL) (cotton candy flavor) for children any age and resistant to the other. If your tolerated drug. Its chemical structure is the same as adults who are not able to swallow the capsules. Can be HIV develops resistance to lamivudine. They are both equally effective and have substituted for Epivir. Epivir or Emtriva, it does an equal safety profile. The only difference is that not mean that your HBV emtricitabine has a longer half-life than lamivudine. is also resistant to them. Emtriva is one of the two drugs in Truvada, which ➤ SEE PACKAGE INSERT for combination with another Both Descovy and Truvada became an alternative to Combivir, the first fixed- more complete informa- hep B drug (such as tenofo- (both contain Emtriva) are dose combination tablet containing zidovudine and tion on potential side vir) to treat the hep B. If you currently recommended lamivudine. It is also in single-tablet regimens such as effects and interactions. are co-infected with HBV by DHHS HIV treatment Atripla, as well as Complera, Stribild, and the newer ➤ TELL YOUR PROVIDER OR and HIV, you should not guidelines for first-time version of these drugs containing TAF, in addition to PHARMACIST about all stop Emtriva without medi- therapy for most people. STRs containing integrase inhibitors (Biktarvy, medications, herbals, cal supervision because it Emtriva is also found in Genvoya). It is also used to treat HBV. and supplements you can cause your HBV to flare several single-tablet regi- are taking or thinking of and cause you to experi- mens (Atripla, Biktarvy, taking, prescribed or not. ence signs and symptoms of Complera, Genvoya, with other antiretrovirals n MANUFACTURER acute hepatitis. HBV should Stribild, Symtuza, and after resistance develops. Gilead Sciences, Inc. n POTENTIAL SIDE EFFECTS be closely monitored by Odefsey). Sometimes, drug Emtriva oral solution should gilead.com AND TOXICITY your provider. Rare skin dis- resistance that the virus be kept in the refrigerator. If (800) GILEAD-5 Emtriva is very well toler- coloration (darkening of the develops against emtric- kept at room temperature, (445–3235) ated. The most common skin on the palms and the itabine makes the virus the oral solution should be side effects (rarely reported) soles) can occur and was reproduce at a slower rate. used within three months. n AVERAGE WHOLESALE PRICE may include headache, diar- more frequent in children, This drug resistance can The capsule is small, which 200 mg, 30 capsules: rhea, and nausea. If you but is generally mild and also improve the antiviral is an advantage for people $643.82/month have HIV and HBV, guide- not concerning. activity of Retrovir (zidovu- with difficulty swallowing. lines recommend treatment dine) and Viread (tenofovir), for both viruses. Emtriva n POTENTIAL DRUG INTERACTIONS and for that reason, some can treat both HIV and No significant drug inter- providers continue Emtriva HBV, but must be used in actions. Emtriva may be treatment in combination

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Epivir lamivudine (3TC) NRTI NUCLEOSIDE REVERSE TRANSCRIPTASE RECOMMENDED AS COMPONENT OF INITIAL REGIMEN FOR MOST PEOPLE INHIBITOR (NUCLEOSIDE, OR “NUKE”) ★ WHEN USED IN COMBINATION WITH DOLUTEGRAVIR AND ABACAVIR n STANDARD DOSE • regimen. Avoid use of sor- DR. DAVID HARDY SAYS: Epivir was approved in One 300 mg tablet once daily (or one 150 mg tablet bitol-containing medicines 1995 as the fourth antiretroviral medication and twice daily), without regard to food. Dosing needs to be with lamivudine; there are nuke. Due to its high potency and excellent tolerability adjusted for adults and children who have decreased many, such as acetamino- (it has virtually no side effects), it has survived for 23 kidney function (creatinine clearance less than 50 mL/ phen liquid (Tylenol liquid years as a commonly used antiretroviral as most other min). See package insert for guidance on dosing in the and others). antiretrovirals approved during that time have fallen setting of kidney impairment. Must be taken in com- by the wayside due to toxicity. It has been available as bination with another antiretroviral(s), which does not n MORE INFORMATION generic lamivudine since 2011. As mentioned on the contain the medication in this drug. Epivir (lamivudine) is Emtriva page, due to their almost identical properties similar to Emtriva (emtric- Emtriva and Epivir are almost interchangeable, includ- According to the package insert, it is indicated for itabine): both treat HIV and ing their high susceptibility to the very common adults and children at least 3 months of age and older. HBV and have the same M184V mutation in the virus. In a 2-drug regimen with Based on pediatric DHHS guidelines, it can be used as resistance profile, meaning Tivicay (see dolutegravir/3TC), Epivir was recently part of an empiric HIV regimen in infants of at least 32 that if your virus is resis- shown to be part of a successful 2-drug, non-protease weeks’ gestation at birth for higher risk perinatal HIV tant to one drug, it will be inhibitor regimen for first-line therapy. exposure. Epivir for children is dosed based on body resistant to the other. If your weight. See the package insert and/or DHHS guidelines HIV develops resistance to ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: for weight-based dosing. lamivudine, it doesn’t mean 0 Epivir, or lamivudine, is the oldest antiretroviral Take missed dose as soon as possible, unless it is that your HBV is also resis- still in use today. It is well tolerated, very effective, closer to the time of your next dose. Do not double up tant to it. Sometimes, drug and has no drug-drug interactions. It has been used in on your next dose. The 150 mg tablets are scored and resistance that the virus combination with other NRTIs like zidovudine may be split. Based on drug properties, tablets may be develops against lamivudine (Combivir) and abacavir (Epzicom) and is a compo- crushed and added to a small amount of semi-solid food makes the virus reproduce nent of the single-tablet regimen Triumeq. It is used or liquid for immediate consumption. Epivir is also avail- at a slower rate. This drug to treat individuals co-infected with HIV and HBV. It able as an oral solution (10mg/mL) (strawberry-banana resistance can also improve seems to work best in combination with other nukes flavor) for children and adults who are not able to swallow the antiviral activity of as the backbone of a regimen. The only downside is the tablets. Can be substituted for Emtriva. Retrovir (zidovudine) and its resistance profile. One mutation (M184V) can Viread (tenofovir), and for reduce its effectiveness. that reason, some providers ➤ SEE PACKAGE INSERT for B drug (such as tenofovir) continue Epivir treatment more complete informa- to treat the hep B. If you in combination with other available as generic lami- name drugs and co-formu- tion on potential side are co-infected with HBV antiretrovirals after resis- vudine, which should be as lations, such as Genvoya or effects and interactions. and HIV, you should not tance develops. Lamivudine effective and well tolerated Triumeq, might be restrict- stop Epivir without medical is also available in sev- as the brand name drug ed to patients who can’t n POTENTIAL SIDE EFFECTS supervision because it can eral combination products: Epivir. Some insurers may physically tolerate generic AND TOXICITY cause your HBV to flare up Cimduo (with tenofovir DF), require patients to take regimens. Epivir is very well toler- and cause you to experi- Combivir (with zidovudine), regimens containing gener- ated. The most common ence signs and symptoms of Epzicom (with abacavir), ics rather than brand name n MANUFACTURER side effects with incidence acute hepatitis. HBV should Trizivir (with zidovudine and drugs, including simpler co- ViiV Healthcare greater than or equal to be closely monitored by abacavir), Symfi and Symfi formulated products. For viivhealthcare.com 15% were headache, diar- your provider. Lo (with tenofovir DF and example, since both zid- (877) 844-8872 rhea, nausea, malaise efavirenz), Delstrigo (with ovudine (Retrovir, AZT) and (general ill feeling), fatigue, n POTENTIAL DRUG INTERACTIONS tenofovir DF and doravirine), lamivudine are available n AVERAGE WHOLESALE PRICE nasal symptoms, diarrhea, No significant drug interac- and Triumeq (with dolute- in generic form, a person Epivir 300 mg tablets, and cough. If you have HIV tions. Epivir may be used gravir and abacavir). Epivir might have to take these 30 tablets: and HBV, guidelines recom- with hepatitis C drugs as part of the combination two generic pills instead of $498.89/month mend treatment for both such as Daklinza, Epclusa, tablet Combivir is recom- the fixed-dose combination generic lamivudine viruses. Emtriva can treat Harvoni, Olysio, Sovaldi, mended as an alternative tablet Combivir. The avail- 300 mg tablets, both HIV and HBV, but Viekira Pak, or Zepatier, NRTI combination com- ability of generics might 30 tablets: $429.19/ must be used in combina- depending on the other ponent of an ART regimen also limit choices of therapy. month tion with another hepatitis components in the HIV during pregnancy. Epivir is For example, newer brand

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Viread tenofovir disoproxil fumarate (TDF) NRTI NUCLEOSIDE REVERSE TRANSCRIPTASE RECOMMENDED AS COMPONENT INHIBITOR (NUCLEOSIDE, OR “NUKE”) ★ OF INITIAL REGIMEN FOR MOST PEOPLE n STANDARD DOSE • n POTENTIAL DRUG INTERACTIONS DR. DAVID HARDY SAYS: Viread was approved in One 300 mg tablet once daily, without regard to food Viread decreases the lev- 2001 as the sixth nuke. Because of its different in adults and children at least 2 years old weighing at els of Reyataz; therefore, HIV resistance mutation pattern, it continued to be least 21 pounds (10 kg). Viread tablets are also avail- Reyataz 300 mg must be potent when other nukes had failed and thus became able in the following dosages: 150 mg, 200 mg, 250 mg boosted with Norvir 100 a common part of most ART regimens from 2001 to tablets, and oral powder (40 mg/g in 60 g packets). mg or Tybost 150 mg 2015. Its most common short-term side effects are Viread tablets can be disintegrated in water, grape (taken together with food) mild nausea, queasiness, and mild diarrhea; on a juice, or orange juice with minor stirring and pressure when used in combination long-term basis it can cause kidney damage and from a spoon. In children, Viread is dosed based on with TDF. Kaletra, Prezista/ weakening of bones (osteoporosis or bone demineral- body weight. See package insert for specific weight- Norvir, and Reyataz/Norvir ization) in a small percentage of PLWH. It is increas- based dosing. Must be taken in combination with increase Viread levels, but ingly being replaced by TAF-containing regimens. another antiretroviral(s) which does not contain the there is no dose adjustment A generic form of Viread became available in the U.S. medication in this drug. needed. Patients taking in December 2017. Kaletra, Prezista/Norvir, or Take missed dose as soon as possible, unless it is closer Reyataz/Norvir with TDF ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: to the time of your next dose. Do not double up on your should be monitored for 0 Viread, or tenofovir disoproxil fumarate (TDF), is next dose. Dosing frequency needs to be adjusted for Viread side effects (includ- potent, well tolerated, and has a long half-life. adults and children with decreased kidney function (for ing kidney disorders) due to Monitoring kidney function is important while taking creatinine clearance, or CrCl, less than 50 mL/min). See the higher TDF levels. Do TDF. It has been shown to cause kidney toxicity as well package insert for guidance on dosing in the setting of not take Viread with adefo- as loss of bone density. These side effects tend to dis- kidney impairment. FDA approved for chronic HBV in vir. Avoid taking Viread with appear when discontinued. It is a component of the patients 12 years and older weighing at least 77 pounds drugs that negatively affect single-tablet regimens Complera and Stribild, as well (35 kg). the kidneys, including as Truvada, a widely used fixed-dose combination as a chronic use or high doses of nuke backbone, and as a prophylaxis for HIV infection. NSAIDS (non-steroidal anti- Its manufacturer has developed an improved version ➤ SEE PACKAGE INSERT for worsening bone pain and inflammatory drugs for pain, of TDF known as TAF (tenofovir alafenamide fuma- more complete informa- fractures, with or without such as Advil or Motrin rate). TAF is a component of the single-tablet regimen tion on potential side muscular pain or weakness, (ibuprofen) and Aleve Genvoya and is replacing TDF in many fixed-dose effects and interactions. as well as any concerning (naproxen). Viread may be combination and single-tablet regimens. changes in urinary habits, used with hepatitis C drugs n POTENTIAL SIDE EFFECTS as these could be signs of such as Daklinza, Harvoni, AND TOXICITY kidney problems. If you Olysio, Sovaldi, Viekira Pak, three single-tablet regimens combination tablets Cimduo Generally well tolerated, have HIV and HBV, guide- or Zepatier, depending on containing TAF instead of and Temixys. Viread as part but some may experience lines recommend treatment the other components in TDF. Descovy is another of the combination tablet nausea, diarrhea, vomiting, for both viruses. Viread can the HIV regimen. Monitor version of Truvada, combin- Truvada is recommended and gas. Decreases in bone treat both HIV and HBV, for tenofovir toxicities if ing emtricitabine with TAF by DHHS as one of the mineral density (BMD) have but must be used in com- used with Epclusa. Tell instead of TDF. In clinical preferred NRTI combina- been observed. BMD moni- bination with another hep B your provider or pharma- trials, TAF had fewer kid- tion components of an ART toring should be considered drug (such as Emtriva) to cist about all medications, ney and bone issues than regimen in pregnancy. in people who have a his- treat the hep B. If you are herbals, and supplements TDF. The NIH reported last tory of bone fracture due to co-infected with HBV and you are taking or thinking of year that infants exposed n MANUFACTURER bone disease or are at risk HIV, you should not stop taking, prescribed or not. in the womb to TDF may Gilead Sciences, Inc. for osteopenia or osteopo- Viread without medical have lower bone mineral gilead.com rosis. Viread may cause supervision because it can n MORE INFORMATION content than those exposed (800) GILEAD-5 kidney toxicities. Creatinine cause your HBV to flare TDF with emtricitabine, to other antivirals. Tenofovir (445-3235) clearance (CrCl) should be and cause you to experi- as Truvada, is a recom- DF was approved in 2012 assessed before initiating ence signs and symptoms of mended NRTI combination as part of Truvada for HIV n AVERAGE WHOLESALE PRICE treatment. In addition to acute hepatitis. HBV should by DHHS HIV treatment prevention as PrEP (pre- 300 mg tablets: CrCl, glucose and protein in be closely monitored by guidelines for first-time exposure prophylaxis; see $1,368.26/month the urine and serum phos- your provider. The Viread therapy. A new version of Truvada for PrEP page). generic 300 mg tablets: phorus should be monitored formulation contains lac- tenofovir, called tenofovir TDF is part of the single- $1215.94/month more often in patients at risk tose, which can cause some alafenamide (TAF), replaced tablet regimens Atripla, for kidney problems. Tell abdominal discomfort, espe- TDF in certain fixed-dose Symfi, Symfi Lo, Complera, your provider about any pain cially in patients sensitive to combinations. Biktarvy, Delstrigo, and Stribild as in extremities, persistent or lactose. Genvoya, and Odefsey are well as the fixed-dose

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Ziagen abacavir (ABC) RECOMMENDED AS COMPONENT OF INITIAL REGIMEN NRTI NUCLEOSIDE REVERSE TRANSCRIPTASE FOR MOST PEOPLE WHEN USED IN COMBINATION WITH INHIBITOR (NUCLEOSIDE, OR “NUKE”) ★ DOLUTEGRAVIR AND LAMIVUDINE (AS TRIUMEQ) n STANDARD DOSE • HSR, abacavir should be DR. DAVID HARDY SAYS: Ziagen was approved Two 300 mg tablets once daily (or one 300 mg tablet stopped and you can never in 1998 as the fifth nuke at a time when HIV twice daily), without regard to food. take abacavir or any prod- resistance to antiretrovirals and treatment failure was uct containing abacavir very common. It provided a new option for treatment For adults and children at least 3 months of age and (Epzicom, Trizivir, Ziagen, at the time it was approved. From the beginning, this older. In children Ziagen is dosed based on body weight. or Triumeq) again (starting medication has had its challenges. As the drug was See the package insert for weight-based dosing. Tablets again is called rechalleng- being studied in the late 1990s, a severe and possibly may be crushed or split and added to a small amount ing). Rechallenging can fatal allergic reaction (hypersensitivity) was discov- of semi-solid food or liquid. Ziagen is also available as cause a rare life-threatening ered. Super elegant (cool) pharmacogenetic studies an oral solution (20 mg/mL) (strawberry-banana flavor) reaction. This does not linked the occurrence of this side effect to a specific for children and adults who are not able to swallow the apply to a missed dose gene (HLA-B*5701). A simple blood or mouth swab tablets. Must be taken in combination with another when there is no HSR, but can be used to detect this gene and determine if a antiretroviral(s) which does not contain the medication in talk with your healthcare PLWH can take the medication safely. Next, a this drug. provider and watch for European cohort study linked Ziagen to heart attacks, Dose adjustment is not needed for people with kidney symptoms if you’ve stopped and a U.S. study showed it to be less potent than impairment. Dose adjustment is needed for people with the drug for a few days, Viread. Despite these challenges, Ziagen has sur- mild liver impairment (200 mg twice daily). Ziagen preferably under the obser- vived, a bit tattered, as a nuke still used today, almost should not be used in people with moderate or severe vation of others who can exclusively in the STR Triumeq. A generic form of liver disease. call for medical help if you Ziagen has been available in the U.S. since 2012. Take missed dose as soon as possible, unless it is develop symptoms. An HSR closer to the time of your next dose. Do not double up on can technically occur at any ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: your next dose. time, regardless of how 0 Abacavir is a nucleoside reverse transcriptase long you have been taking inhibitor drug used for the treatment of HIV infection the medication, however, it in combination with other HIV medicines. Serious side ➤ SEE PACKAGE INSERT for com). If the HLA-B*5701 is much more likely to occur effects of abacavir include allergic reactions, a build- more complete informa- test is positive, you are at when you start (or re-start) up of acid in the blood (lactic acidosis), and liver prob- tion on potential side an increased risk for HSR the medication (90% occur lems. If when taking abacavir you find yourself having effects and interactions. and you should not take within the first 6 weeks of an allergic reaction, stop the drug immediately and abacavir. An allergy to it treatment). call your doctor. This hypersensitivity reaction can n POTENTIAL SIDE EFFECTS should be entered in your Some large observa- cause death. Your risk for this reaction is high if you AND TOXICITY medical record. A negative tional studies suggest aba- have a specific gene variation, which can be deter- The length of this section HLA-B*5701 test does not cavir may increase the risk mined by a blood test prescribed by a doctor. is meant to be informa- mean you won’t have HSR, of cardiovascular events, tive, not scary. The most but the risk is very low including myocardial infarc- common side effects with (1% from clinical studies). tion (MI, or heart attack), taking or thinking of taking, simple test reveals whether an incidence greater than Symptoms of HSR usually in people with risk factors prescribed or not, as there you are at high risk for 10% were nausea, head- include some combination (such as older age, smoking, are other drug interactions the allergic reaction. FDA ache, malaise (general ill of the following: fever, skin diabetes, high blood pres- which are not listed here. researchers reported find- feeling), fatigue, vomiting, rash, malaise (general ill sure, high cholesterol, fam- ing a mechanism for auto- and dreams/sleep disorders. feeling), severe nausea, ily history of heart disease, n MORE INFORMATION immune drug reactions, In pediatric patients, the headache, muscle ache, and drug use), especially The ACTG A5202 study including abacavir HSR, more common side effects chills, diarrhea, vomiting, within the first 6 months found that abacavir/lamivu- and hope it helps improve were fever and/or chills, abdominal pain, respiratory of therapy. However, other dine (Epzicom) was inferior drug safety in the future. nausea and vomiting, skin symptoms (cough, difficulty studies, including a large to tenofovir/emtricitabine Ziagen as part of the com- rashes, and ear/nose/throat breathing, sore throat), and/ meta-analysis, have shown (Truvada) in getting people bination tablet Epzicom is infections. or joint pain. Symptoms are no increase in cardiovascu- undetectable when their recommended by DHHS as Approximately 8% of listed on the patient infor- lar risk. To date, no consen- pre-treatment viral load one of the preferred NRTI people who took abacavir mation sheet and warning sus has been reached on was over 100,000 copies/ combination components in clinical trials (where card that you receive each the association of abacavir mL. However, when com- of an ART regimen during screening for HLA-B*5701, time you fill your prescrip- with cardiac risk or a pos- bined with Tivicay (dolute- pregnancy. a genetic marker associated tion. You should keep the sible mechanism for the gravir), Epzicom performed with abacavir hypersensi- warning card with you. HSR association. People who just as well as Truvada n MANUFACTURER tivity, was not performed) might be confused with flu, are at high risk for heart in people with high viral ViiV Healthcare experienced hypersensi- but symptoms of HSR usu- disease should discuss risks loads (over 100,000 cop- viivhealthcare.com tivity reaction (HSR), an ally worsen, very slowly, with their provider and they ies/mL). Hence, Triumeq is (877) 844-8872 allergic-like reaction. To and with every dose. should be monitored more the only abacavir-containing minimize the risk for HSR, a People who think they closely. regimen recommended by n AVERAGE WHOLESALE PRICE blood test for HLA-B*5701 are experiencing HSR must DHHS as initial therapy for Ziagen should be done prior to be evaluated by an experi- n POTENTIAL DRUG INTERACTIONS most HLA-B*5701 negative 300 mg tablet, 60 tablets: starting an HIV regimen enced HIV provider right Alcohol can increase aba- people. It is recommended $670.37/month containing abacavir to iden- away before they stop tak- cavir levels and therefore that people with symptoms generic abacavir tify patients at higher risk ing abacavir. Do not use a can increase the possibility of acute respiratory dis- 300 mg tablet, 60 tablets: for this reaction. This test skin patch test to confirm of side effects. Tell your pro- ease consider HSR even if $602.71/month is covered by most insur- HSR. Symptoms usually vider or pharmacist about another diagnosis such as ance and also by LabCorp/ resolve after permanent dis- all medications, herbals, pneumonia, bronchitis, or ViiV (go to viivconnect. continuation. If you develop and supplements you are flu is possible. But again, a

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Edurant rilpivirine (RPV) RECOMMENDED AS COMPONENT OF INITIAL REGIMEN NNRTI NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR IN CERTAIN CLINICAL SITUATIONS IN COMBINATION WITH (NON-NUCLEOSIDE, OR “NON-NUKE”) ✔ DESCOVY OR TRUVADA (AS ODEFSEY OR COMPLERA) n STANDARD DOSE • Tagamet, Zantac, and Axid) DR. DAVID HARDY SAYS: Edurant was approved One 25 mg tablet once daily with a standard meal (more should be taken 12 hours in 2011 as the second “second generation” than 390 calories). For adults and children 12 years of before or four hours after NNRTI to be used as an ART regimen in treatment- age and older weighing at least 77 pounds (35 kg). Must an Edurant dose. If admin- naïve PLWH. Its upside is its excellent tolerability be taken in combination with another antiretroviral(s) istered with rifabutin, the (side effects occur uncommonly); its downside is that which does not contain the medication in this drug or dose of Edurant should be it lacks potency for PLWH with high viral loads medication from the same drug class. No dose adjust- increased to two 25 mg (greater than 100,000 copies/ml). Edurant has been ment needed for pregnant patients with undetectable tablets once daily with a used in three STRs, Complera, Juluca, and Odefsey viral load on a stable rilpivirine-based regimen, but meal. When rifabutin is (see those pages). Due to its potency concerns, it has monitor viral load closely because lower rilpivirine drug stopped, Edurant dose never been considered the best choice for all PLWH exposure has been seen during pregnancy. should be decreased to starting their first ART regimens, but only those with 25 mg daily. Monitor for lower viral loads (less than 100,000 copies/mL). Viral load (HIV RNA) must be less than 100,000 worsening of any fungal copies/mL and CD4 T-cell count must be above 200 infections when Edurant ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: cells/mm3 before starting Edurant due to higher rates is used with antifungal 0 Rilpivirine is an NNRTI shown not to be inferior of virologic failure in these patients. medications like fluconazole, to efavirenz in individuals with a viral load less than Take missed dose as soon as possible with a meal, itraconazole, ketoconazole, 100,000. It was first approved as a single agent but unless it is closer to the time of your next dose. Do not posaconazole, and voricon- nowadays it is used in various single-tablet regimens: double up on your next dose. azole; dose adjustment for Complera, Odefsey, and Juluca. The resistance profile Must be taken with a meal that you chew—not just these medications may be of this drug is complicated. If resistance to rilpivirine nutritional drinks or protein shakes. Taking rilpivirine needed. Use azithromycin develops, cross-resistance to Intelence (etravirine) without food could result in a 40% decrease in drug when possible instead of occurs. It is well tolerated and needs to be taken with absorption and may lead to resistance. the antibiotics clarithro- food. It works well when used to switch regimens in mycin, erythromycin, and individuals who have an undetectable viral load. It is telithromycin. Methadone important to know the drug-drug interactions of rilpi- ➤ SEE PACKAGE INSERT for triglycerides when com- levels are reduced slightly virine. It should not be taken with antacids because it more complete informa- pared to Sustiva. Edurant and patients should be will affect drug absorption. Rilpivirine plus cabotegra- tion on potential side improved HDL (“good”) monitored for symptoms of vir is under investigation as a once-a-month long-act- effects and interactions. cholesterol slightly less than withdrawal. Should be used ing fixed-dose HIV treatment. Sustiva. Liver problems can with caution when taken n POTENTIAL SIDE EFFECTS occur with Edurant (even in with other medications AND TOXICITY patients without a history of with a known risk of tors- greater than 100,000 cop- commonly found in some Moderate to severe liver disease). Edurant can ades de pointes or QT pro- ies/mL or CD4 less than other countries, an NNRTI side effects are uncom- cause a small, reversible longation (these abnormal 200 cells/mm3. A rilpiv- would not be recommended mon. Most common side increase in kidney func- heart rhythms can make irine-based regimen may as HIV-2 is inherently resis- effects occurring in 3–5% tion test (serum creatinine) the heart stop). No dose be advantageous in people tant to NNRTIs. Edurant can of study subjects were within the first few weeks of adjustment needed with with high risk for heart be used during pregnancy, insomnia, headache, rash, treatment without affecting hepatitis C medications disease due to its relatively and is listed as a DHHS and depressive disorders. actual kidney function. Daklinza, Epclusa, Harvoni, low impact on lipid profile. alternative NNRTI to use in Tell your doctor right away Olysio, Sovaldi, or Zepatier. While its tolerability and pregnancy in combination if you experience feelings n POTENTIAL DRUG INTERACTIONS Cannot be taken with safety profiles are advantag- with a two-NRTI backbone. of sadness, hopelessness, Edurant cannot be taken Viekira Pak. Tell your pro- es for Edurant, the greater According to the FDA, lower anxiety or restlessness, or with the anti-seizure medi- vider or pharmacist about potential for virologic failure exposures of rilpivirine were have suicidal thoughts cations carbamazepine, all medications, herbals, in patients with high viral observed during pregnancy, or actions. A small study oxcarbazepine, phenobar- and supplements you are loads or low CD4 counts, therefore, viral load should showed a higher rate of bital, or phenytoin; the taking or thinking of taking, food restrictions, and cross- be monitored closely. depressive disorders in ado- anti-TB drugs rifampin prescribed or not, as there resistance to the other lescents (19.4%—seven and rifapentine; proton are other drug interactions NNRTIs puts Edurant at a n MANUFACTURER out of 36 youths—vs. 9% pump inhibitors (Aciphex, which are not listed here. disadvantage for first-time Janssen Therapeutics for adults), which may or Dexilant, Nexium, Prevacid, treatment—people may not edurant.com may not have been related Protonix, and Prilosec); or n MORE INFORMATION be able to switch to another (800) JANSSEN to Edurant. Two different the herb St. John’s wort. Do A new medication com- NNRTI if their HIV develops (526-7736) studies comparing Edurant not take with more than one bining rilpivirine with NNRTI resistant mutations to Sustiva showed that systemic dose of the steroid dolutegravir was approved to Edurant. Data for use of n AVERAGE WHOLESALE PRICE Edurant was slightly better dexamethasone. Antacids by the FDA in late 2017; rilpivirine in combination $1,338.13/month tolerated. Edurant also has should be taken two hours see Juluca. Edurant is not with an abacavir/lamivudine minimal negative effects before or at least four recommended for treat- background are insufficient on LDL (“bad”) choles- hours after Edurant. Acid- ment-naïve patients with to recommend at this time. terol, total cholesterol, and reducing drugs (Pepcid, a pre-treatment viral load For individuals with HIV-2,

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Pifeltro doravirine (DOR) NNRTI NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR RECOMMENDED AS COMPONENT OF (NON-NUCLEOSIDE, OR “NON-NUKE”) ✔ INITIAL REGIMEN IN CERTAIN CLINICAL SITUATIONS n STANDARD DOSE • was superior to boosted DR. DAVID HARDY SAYS: Pifeltro was FDA One tablet once daily without regard to food. Tablet darunavir at week 96 in approved in August 2018 and is also considered contains 100 mg of doravirine. Must be taken in com- terms of virologic suppres- to be a “second generation” NNRTI due to its bination with another antiretroviral(s) which does not sion, but it should be noted enhanced resistance profile compared to Sustiva and contain the medication in this drug or medication from there was a higher rate other older “first generation” NNRTIs. In fact, lab the same drug class. of study discontinuation studies predict that it may be effective after a first in the boosted darunavir generation NNRTI has failed and left HIV resistance Approved only for adults at this time. Take missed group. Doravirine is a non- mutations. To date, data from two large clinical trials dose as soon as possible, unless it is closer to the time nucleoside medication, and comparing doravirine to Sustiva and to Prezista/ of your next dose. Do not double up on your next dose. it should be noted that Norvir have shown that Pilfeltro has similar anti-HIV No dosage adjustment necessary for mild, moderate, or this class of drugs typi- potency as those two known potent medications and severe kidney impairment or for mild or moderate liver cally has a lower barrier to fewer side effects. Pifeltro is also approved (August impairment. Pifeltro has not been studied in patients with resistance as well as have 2018) as an STR combining it with generic tenofovir severe liver impairment. extensive cross-resistance. DF and lamivudine (see Delstrigo). Additionally, the emergence of resistance at the time of ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: ➤ SEE PACKAGE INSERT for the anticonvulsants carba- virologic failure has been 0 Pifeltro is the new Merck once-a-day stand- more complete informa- mazepine, oxcarbazepine, reported with doravirine. alone non-nucleoside reverse transcriptase inhibitor tion on potential side phenobarbital, and phenyt- Despite the side effects used to treat HIV in combination with other HIV medi- effects and interactions. oin; the androgen receptor listed above, doravirine cines. Pifeltro is contained in the single-tablet regi- inhibitor enzalutamide; the has tolerability advantages men Delstrigo. This treatment is contraindicated with n POTENTIAL SIDE EFFECTS antimycobacterials rifampin over efavirenz and has rela- medications that are metabolized by the P450 AND TOXICITY and rifapentine; the cyto- tively favorable lipid effects enzyme inducer. This enzyme causes a significant Most common side effects toxic agent (cancer drug) when compared with both decrease in doravirine plasma levels and low plasma (at least 5% of people tak- mitotane; and the herbal St. boosted darunavir and levels decrease its effectiveness. ing it) observed with Pifeltro John’s wort. Tell your pro- efavirenz. It also has fewer in studies were nausea (7%), vider or pharmacist about potential drug interactions dizziness (7%), headache all medications, herbals, than efavirenz or rilpivirine, Only 1 of 364 doravirine- n MANUFACTURER (6%), fatigue (6%), diarrhea and supplements you are and, unlike rilpivirine, viro- treated patients developed Merck and Co. (5%), abdominal pain (5%), taking or thinking of taking, logic efficacy is not com- drug resistance, a low num- (800) 622–4477 abnormal dreams (1%), and prescribed or not, as there promised in those with high ber for an NNRTI; there pifeltro.com increased bilirubin (5%). are other drug interactions baseline viral loads or low was no resistance noted Rash, which is a common which are not listed here. CD4 counts. Doravirine has in the boosted daruna- n AVERAGE WHOLESALE PRICE side effect of the NNRTIs, not been directly compared vir group. See more data $1,656.00/month was reported in up to 2% of n MORE INFORMATION to integrase inhibitor-based online. Merck has applied the studied population. In Received FDA approval regimens in clinical trials to the FDA for a switch indi- one study (DRIVE-AHEAD), in 2018. Doravirine may yet. Because there were cation, so that people with an in-depth analysis was be an option for patients significantly fewer people undetectable viral load on conducted of the incidence who have developed drug who received doravirine + their current treatment can of neuropsychiatric adverse resistance to other NNRTIs. Epzicom compared to those switch to a Pifeltro-based events associated with a A single-tablet regimen who received Truvada, the regimen. doravirine-containing regi- (STR) containing doravirine guidelines consider Pifeltro men (Delstrigo) compared was also approved last plus Epzicom to be an to Atripla. Neuropsychiatric year; see Delstrigo page. option for initial therapy events, such as depression, Delstrigo, however, con- but the guidelines panel sleep disturbances, and diz- tains the older version of has less confidence in ziness, are another common tenofovir, tenofovir DF. The this regimen than in the side effect of the NNRTI stand-alone Pifeltro allows other doravirine-containing class. See data online. people to take it with the regimens. There is no data Doravirine did not appear to newer and less toxic teno- on the safety of doravirine negatively affect cholesterol fovir alafenamide, or TAF use in pregnancy. In the in studied populations. (found in Descovy). On the DRIVE-FORWARD study, other hand, of course, the comparing doravirine to n POTENTIAL DRUG INTERACTIONS use of Pifeltro means the darunavir, the treatment- New interactions continue necessity for an extra pill naïve individuals in the to be discovered after drug of Descovy, or maybe more study were 80% (darunavir approval. When using with than one extra pill, depend- group) and 84% (doravirine the antibiotic drug rifabu- ing on the regimen being group) undetectable (less tin (used for TB and MAC used. Merck has applied to than 50 copies viral load). treatment), increase the the FDA for a switch indi- That’s a lower success rate Pifeltro dose to one tablet cation, so that people with than is expected in HIV twice a day, approximately undetectable viral load on treatment today, but was every 12 hours. The follow- their current treatment can thought to be affected by ing are among the medica- switch to a Pifeltro-based the number of people who tions that may lower the regimen. Pifeltro was found quickly dropped out of the blood levels of Pifeltro, and to be non-inferior to boost- study when they saw how therefore may decrease its ed darunavir (Prezista) as many pills they had to effectiveness, and should well as efavirenz (Sustiva) take. Those drop-outs were not be used with Pifeltro: at 48 weeks. Doravirine counted as virologic failures.

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GENERIC IS AVAILABLE.

efavirenz (EFV) Sustiva RECOMMENDED AS A COMPONENT OF INITIAL REGIMEN IN CERTAIN CLINICAL SITUATIONS (AS A NNRTI NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR COMPONENT OF ATRIPLA, SYMFI, OR SYMFI LO, OR IN (NON-NUCLEOSIDE, OR “NON-NUKE”) ✔ COMBINATION WITH DESCOVY OR TRUVADA) n STANDARD DOSE • interactions not listed here. DR. DAVID HARDY SAYS: Approved in 1998, One 600 mg tablet once daily, preferably on an empty Do not take with midazolam, Sustiva was the “queen bee” of antiretrovirals stomach at bedtime. Must be taken in combination pimozide, ergot deriva- as the “kinder and gentler” alternative to the highly with another antiretroviral(s) which does not contain tives, St. John’s wort, or potent but difficult to tolerate protease inhibitors the medication in this drug or medication from the triazolam. May affect war- until the appearance of the integrase inhibitors in same drug class. farin levels. Can decrease 2007. Although highly potent against HIV and taken levels of buprenorphine just once daily, the unique side effects of grogginess, Approved for adults and children 3 months and older and methadone—monitor dizziness, and vivid dreams were often treatment-lim- weighing at least 7.7 pounds (3.5 kg). For children for withdrawal. Increase iting side effects for many PLWH. It was thought that weighing less than 88 pounds (40 kg), the dose is based Kaletra to two 200/50 mg these side effects would go away over time, but long- on weight. See the package insert for specific weight- tablets plus one 100/25 term studies with Sustiva (up to 5 years) showed that based dosing. For children weighing at least 88 pounds, mg tablet twice daily (total they never improve for some PLWH. Worsening of use the standard adult dose. For those who can’t swallow 500/125 mg twice daily) mental health conditions and increased suicidal capsules, administer by capsule sprinkle method. See with food when taken with thoughts and attempts have limited Sustiva’s use. It is below or drug label for instructions or watch video at Sustiva. Kaletra cannot still the most commonly prescribed antiretroviral in sustiva.com. be taken once daily with the world, although this is starting to change. Take missed dose as soon as possible, unless it is closer Sustiva. When using with in time to your next dose. Do not double up on your next Tivicay, increase the Tivicay ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: dose. Also available in 50 mg and 200 mg capsules. dose to 50 mg twice daily. 0 Efavirenz is a very potent and long-acting anti- Use with caution in mild liver impairment; not recom- Treatment-experienced peo- viral. Sustiva is the anchor drug of Atripla, the first mended with moderate or severe liver impairment. ple should not take Reyataz and most widely used single-tablet regimen for the with Sustiva, but for treat- last 11 years. Sustiva’s central nervous system side ment-naïve people, Reyataz effects are challenging. Dizziness, weird dreams, ➤ SEE PACKAGE INSERT for is more common and more once-daily dose should be depression, and feeling tired constantly are some of more complete informa- severe. Efavirenz may raise 400 mg with Norvir boost. the side effects reported. Some individuals tolerate it tion on potential side levels of triglycerides (fat Boost once-daily Lexiva well and others manage to overcome them after three effects and interactions. in the blood) and choles- 1,400 mg with 300 mg months. Other NNRTIs and INSTIs with no CNS side terol. Efavirenz can cause a Norvir. No change in the effects, as effective and way more tolerable have n POTENTIAL SIDE EFFECTS false positive for marijuana ritonavir dose is required been developed. AND TOXICITY on certain drug tests. A when efavirenz is adminis- Central nervous system more specific confirmatory tered with Lexiva plus rito- (CNS) symptoms (dizziness, test can be done. A link navir twice daily. Increase monitored when starting or HIV guidelines, Sustiva was insomnia, impaired concen- to birth defects in humans Selzentry to 600 mg twice stopping Sustiva. Cardizem, downgraded in 2017 from tration, abnormal or vivid has not been supported in daily. Increase the Sustiva Lipitor, Pravachol, and “preferred” to an “alternative” dreams, and hallucinations) meta-analyses. The preg- dose to 800 mg once daily Zocor doses may need to component of an initial regi- are most common at the nancy recommendation is with rifampin for people be adjusted. Titrate dose men for children ages 3–12 start of treatment and usu- that women in their first weighing 110 pounds (50 of bupropion and sertraline years. For individuals with ally diminish in two to four trimester continue taking kg) or more. Rifabutin can based on clinical response. HIV-2, commonly found in weeks. Bedtime dosing on efavirenz as long as their be used as an alternative, Should not be taken with some other countries, an an empty stomach can help viral load remains undetect- but dose adjustment is other medications that NNRTI would not be recom- reduce symptoms. Less able; however, efavirenz needed. When taken with prolong QT interval or mended as HIV-2 is inher- common psychiatric symp- should only be used if the carbamazepine, phenobar- medications with a known ently resistant to NNRTIs. toms (catatonia, depression, potential benefit outweighs bital, or phenytoin, periodic risk of torsades de pointes. Efavirenz is found in the suicidal thoughts or actions, the potential risk, as when monitoring of anticonvulsant No dose adjustment single-tablet regimens aggression, paranoid/manic other treatment options and Sustiva levels should with Harvoni or Sovaldi. Atripla, Symfi, and Symfi reactions) may also occur. are not available. Because be done or alternative Increase Daklinza dose to Lo; see those pages. A 2014 study reviewed of the association with anti-seizure drugs, such as 90 mg with Sustiva. Don’t four previously published suicidality and neuropsy- levetiracetam, should be take with Epclusa, Olysio, n MANUFACTURER AIDS Clinical Trials Group chiatric effects, it is also considered. Effectiveness Viekira Pak, or Zepatier. Tell Bristol-Myers Squibb (ACTG) studies regarding recommended to screen for of birth control pills may your provider or pharmacist bms.com efavirenz and suicidal ide- antenatal and postpartum be decreased; consider about all medications, herb- sustiva.com ation and re-emphasized depression in women with the use of other contracep- als, and supplements you (800) 321-1335 the fact that efavirenz has HIV who are taking a regi- tives. Closer monitoring are taking or thinking of an association with sui- men containing efavirenz. and dose adjustments may taking, prescribed or not, n AVERAGE WHOLESALE PRICE cidality (reported suicidal Regular monitoring for be required with posacon- as there are other drug 600 mg tablets: ideation or attempted or increased liver enzyme lev- azole (avoid unless benefit interactions which are not $1,176.74/month completed suicide), and els is recommended initially outweighs potential risk) listed here. generic: $1,117.90/month should be used with cau- and during treatment for and itraconazole. The dose tion in patients with severe people with hepatitis B/C or of voriconazole should be n MORE INFORMATION or uncontrolled depression liver disease. increased to 400 mg every If you can’t sleep, ask and/or a history of suicid- 12 hours and the Sustiva your doctor about gradually ality. It is recommended n POTENTIAL DRUG INTERACTIONS dose should be decreased adjusting the timing of your for anyone on a regimen Tell your provider or phar- to 300 mg once daily using dose until it’s taken during containing efavirenz to be macist about all medica- capsules; tablets should not the day. A rare genetic trait screened for depression and tions, herbals, supplements, be broken. Monitor effec- affecting drug metabolism suicidality. Additional side and over-the-counter prod- tiveness of clarithromycin or of Sustiva, leading to a effects may include rash, ucts you are taking or think- consider using azithromycin higher rate of side effects, nausea, vomiting, diarrhea, ing of taking, prescribed or instead. Levels of immu- occurs more in African and fever. Rash in children not, as there are other drug nosuppressants should be Americans. In pediatric positivelyaware.com/sustiva POSITIVELY AWARE MARCH+APRIL 2019 59 2019 POSITIVELY AWARE HIV DRUG GUIDE

Intelence etravirine (ETR) FOR TREATMENT-EXPERIENCED PATIENTS NNRTI NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR WITH VIRAL STRAINS RESISTANT TO AN NNRTI (NON-NUCLEOSIDE, OR “NON-NUKE”) ✔ AND OTHER ANTIRETROVIRAL DRUGS ONLY n STANDARD DOSE • without a boosted PI and DR. DAVID HARDY SAYS: Approved in 2008 as One 200 mg tablet, twice daily with food. Approved for 150 mg twice daily when the first “second generation” NNRTI due to its adults and children 2 years and older weighing at least used with a boosted PI. improved resistance profile, Intelence has generally 22 pounds (10 kg). See the package insert for specific Do not take Intelence with been used only for PLWH whose HIV has a significant weight-based dosing in children. Also available in 25 Tegretol, Luminal, Dilantin, amount of resistance to other antiretroviral medica- mg and 100 mg tablets. Must be taken in combination Priftin, Rifadin, or the tions. It is approved to be given only on a twice-daily with another antiretroviral(s) which does not contain herb St. John’s wort. Use basis and generally best with boosted Prezista with or medication from the same drug class. with caution when com- without an integrase inhibitor. It is not approved to be bined with the antifungals used in a first-time ART regimen, although a couple of Take missed dose as soon as possible, unless it is Diflucan and Vfend. Dose small studies have shown that it can work. closer to the time of your next dose. Do not double up on adjustments of the antifun- your next dose. People unable to swallow pills (Intelence gals ketoconazole, itracon- ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: tablets are “chalky”) can dissolve tablets in 1 teaspoon azole, and posaconazole 0 Etravirine is a second-generation NNRTI (5 mL) of water or at least enough liquid to cover the may be needed. Dosage that has shown significant viral load reduction in medication, stir well until the water turns milky, add more adjustments of certain cho- individuals who developed resistance to the first water if desired—use orange juice or milk as an alterna- lesterol medications may generation of NNRTIs (efavirenz and nevirapine). Like tive, always placing tablets in water first. Avoid warm be needed based on clinical other NNRTIs, etravirine’s drug-drug interactions are (over 104° F) or carbonated beverages. Drink immedi- response, including Lipitor, many and complicated. It is important to understand ately, rinse the glass several times with water, orange Lescol, Mevacor, Livalo, the interactions and inform the doctor of all over-the- juice, or milk and completely swallow the rinse each time and Zocor. Monitor the counter medications, supplements, and herbals. They to make sure the entire dose is taken. Taking Intelence effectiveness of Coumadin might affect the absorption of etravirine. It is well without food could result in a 50% decrease in the drug (warfarin) and adjust dose tolerated but may cause some rare side effects like absorption and may lead to HIV drug resistance as needed based on clinical rash or increased cholesterol. It is a good second-line response. Alternatives to alternative for treatment-experienced people. The Plavix should be considered size of the pill makes it hard to swallow and it leaves ➤ SEE PACKAGE INSERT for malaise [general ill feeling], when used with Intelence. a chalky taste in the mouth. There is the option of more complete informa- fatigue, muscle or joint Alternatives to clarithromy- dissolving it in water. tion on potential side aches, blisters, oral lesions, cin, such as azithromycin, effects and interactions. conjunctivitis, facial edema, should be considered for ➤ TELL YOUR PROVIDER OR hepatitis, eosinophilia, or treatment of MAC. Lower Taking with Olysio, Viekira highly treatment-experi- PHARMACIST about all angioedema). Levels of liver Valium dose may be needed. Pak, or Zepatier is not enced patients was suc- medications, herbals, enzymes called transami- Use caution with systemic recommended. cessful in getting many and supplements you nases should be monitored. dexamethasone or consider patients to undetectable. are taking or thinking of Rash is associated with all alternatives. Intelence can n Some patients complain taking, prescribed or not, MORE INFORMATION as there are other drug of the current NNRTIs, but be taken with Mycobutin For patients who have of hard-to-swallow, large interactions which are if you develop a rash from 300 mg daily; however, it had virologic failure on an chalky pills; see dissolving not listed here. Intelence, you may still be should be avoided by those NNRTI-containing regimen, instructions in dose section able to take one of the other who are also taking a boost- do not use Intelence in com- or package insert. For indi- NNRTIs. ed PI. Intelence can be bination with a nucleoside viduals with HIV-2, com- n POTENTIAL SIDE EFFECTS n POTENTIAL DRUG INTERACTIONS safely combined with meth- backbone alone. Although monly found in some other AND TOXICITY If Intelence is taken in adone or buprenorphine taking once daily is not FDA countries, an NNRTI would Generally well tolerated, combination with a prote- with additional monitoring approved, some providers not be recommended as but most common side ase inhibitor, the PI must for potential signs of with- are prescribing Intelence HIV-2 is inherently resistant effects include rash as well be boosted with low-dose drawal. Intelence can also once daily (2 of the 200 to NNRTIs. as numbness, tingling, or Norvir. Avoid Intelence with be safely combined with mg tablets) based on clini- pain in the hands or feet. boosted Aptivus or Lexiva. Viagra, Cialis, and Levitra, cal trials that showed that n MANUFACTURER Rare side effects include It should be avoided with though a dosage adjust- once-daily Intelence was Janssen Therapeutics severe rash and peripheral Tivicay unless administered ment of Viagra may be nec- not inferior to Sustiva-based intelence.com neuropathy. Discontinue with one of the following essary. Can be taken with regimens. In Europe, it is (800) JANSSEN Intelence immediately if combinations: Reyataz/ Daklinza (increase Daklinza approved as a once-daily (526-7736) signs or symptoms of severe Norvir, Prezista/Norvir, or dose to 90 mg). Interactions medication. The once-daily skin reactions or hypersen- Kaletra. Taking it in com- with Sovaldi and Harvoni dosing may improve patient n AVERAGE WHOLESALE PRICE sitivity reactions develop bination with Selzentry have not been studied; adherence. The TRIO study 200 mg tablets, (including, but not limited to, requires a Selzentry dose but based on the metabo- reported the combination 60 tablets: $1,628.03/ severe rash or rash accom- adjustment to 600 mg lism, a clinically significant of Intelence with Prezista/ month panied by fever, general twice daily when used interaction is not expected. Norvir and Isentress in

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Selzentry maraviroc (MVC) EI ENTRY/ATTACHMENT INHIBITOR: NOT RECOMMENDED ENTRY INHIBITOR: CCR5 ANTAGONIST ▼ AS COMPONENT OF AN INITIAL REGIMEN n STANDARD DOSE • Fuzeon, and all of the NRTIs DR. DAVID HARDY SAYS: Selzentry was approved The recommended dose varies depending on other and medications that do not in 2007 for PLWH with highly drug-resistant HIV medications being taken but will be either 150, 300, affect the levels of Selzentry; and for first-time ART treatment in PLWH in 2009. or 600 mg twice daily (available in 150 mg and 300 and 600 mg twice daily Selzentry was the second antiretroviral in the entry mg tablets). Approved for adults and children at least if taken with medications inhibitor class to be approved (the first was Fuzeon in two years old weighing at least 22 pounds (10 kg) and that decrease the levels of 2003). Selzentry works uniquely by blocking the CCR5 having a creatinine clearance of at least 30mL/min Selzentry, such as Atripla, receptor on the surface of CD4+ T cells to which HIV (measurement of kidney function); dose depends on Sustiva, Intelence, rifampin, must attach to infect these cells. It stops HIV infection weight. Available in a 20 mg/mL oral solution as well and some anti-convulsants before it enters the cell. Despite favorable study as 25 mg and 75 mg tablets. The oral solution should such as carbamazepine results, primarily in treatment-experienced PLWH, and be administered using the included press-in bottle (Tegretol), phenobarbital, an excellent safety profile, Selzentry use has been lim- adapter and oral dosing syringe. Can be taken without and phenytoin (Dilantin). ited in the U.S. due to a costly and slow turn-around regard to food. Must be taken in combination with Likely dose with rifapentine blood test which must be used to check for suscepti- another antiretroviral(s). is 600 mg twice daily, but bility to the drug and poor results in subsequent clini- use with caution. Not rec- cal trials in PLWH starting first-line treatment. It is Take missed dose as soon as possible, unless it is ommended with St. John’s being studied as a possible treatment for HIV closer in time to your next dose. Do not double up on wort. Selzentry may be co- Associate Neurocognitive Disease (HAND). your next dose. Before you start Selzentry, you will need administered with the hepa- a specific blood test called a Trofile to determine if this titis C medications Sovaldi, ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: medication will work for you. Olysio, Harvoni, and 0 Selzentry, or maraviroc, is an entry inhibitor. It Daklinza at a dose of 300 is a CCR5 antagonist that blocks one of the two mg twice daily; however, receptors (CCR5) on the outside of the CD4 used by ➤ SEE PACKAGE INSERT for hypotension.” Stop taking ledipasvir (in Harvoni) may the virus to enter and infect the cell. People living more complete informa- Selzentry and contact your have potential to increase with HIV need to have a tropism test that will deter- tion on potential side provider right away if you Selzentry levels. Tell your mine if the CCR5 receptor is active. In treatment- effects and interactions. develop a rash, yellowing provider or pharmacist experienced patients HIV may adapt to target CXCR4. of your eyes or skin, dark about all medications, herb- When this occurs, individuals are unable to benefit n POTENTIAL SIDE EFFECTS urine, vomiting, or upper als, and supplements you from a CCR5 inhibitor. Even though it is not as popular AND TOXICITY stomach pain. Selzentry are taking or thinking of as expected, it has become an important option for The most common side should not be used by taking, prescribed or not, those who need add extra help to create an HIV regimen. effects occurring in greater people with severe or end- as there are other drug than 8% of studied patients stage kidney disease who interactions which are not include cough, upper respi- are taking medications listed here. resistance. See ibalizumab does not cause a shift to X4 ratory tract infections, bron- that can affect the levels of page. A tropism assay or negatively affect disease chitis, fever, rash, muscle Selzentry (check with your n MORE INFORMATION (Trofile, Trofile DNA, or progression or CD4 count in and joint pain, flatulence, provider). Selzentry affects Not recommended by HIV-1 Coreceptor Tropism people whose virus can use bloating and distention, immune system cells and DHHS as a component of with Reflex to UDS) is dual-mix. The tropism test abdominal pain, dizziness, could possibly increase the an initial regimen due to needed to determine if this needed is now generally and trouble sleeping. Other risk of infections and cancer, requirement of CCR5 tro- medication will work for paid for by public health less common side effects although this has not been pism prior to initiation of you. Results of a pheno- departments, Medicare, may include allergic reac- observed in studies up to therapy, lack of virologic typic tropism test (Trofile and private insurances. ViiV tions, liver toxicity, and five years of follow-up, and benefit when compared or Trofile DNA) may take may cover the payment for heart problems in those some data indicate it may to other recommended up to a month to complete. the Trofile test under certain with a history of heart be beneficial in cancer or for regimens, and because it Genotypic tests are also circumstances. Selzentry disease. Rarely, Selzentry preventing metastasis (the requires twice-daily dosing. available and may provide seems to have minimal can cause dizziness or spread of cancer to other Selzentry is generally a faster and less expensive impact on lipid levels. Not fainting when standing up parts of the body). recommended only when alternative. Selzentry only recommended for preg- due to low blood pressure. other HIV medications from works for those people with nant women on initial HIV In March 2014, the FDA n POTENTIAL DRUG INTERACTIONS other classes cannot be CCR5-tropic virus. Viral medication. updated the Selzentry label, Dose adjustments with used or when a new class tropism refers to the types stating, “Caution should be other medications and anti- of medication is needed to of HIV that a person can n MANUFACTURER used when administering HIV drugs include: 150 mg construct a complete and have, CCR5 (R5), CXCR4 ViiV Healthcare Selzentry in patients with a twice daily if taken with durable treatment regimen (X4), or Dual-Mix Tropic viivhealthcare.com history of or risk factors for medications that increase for patients who have drug (R5 and X4). Selzentry selzentry.com postural hypotension, car- the levels of Selzentry, such resistance. Complex dos- blocks CCR5, a receptor on (877) 844-8872 diovascular comorbidities, as boosted protease inhibi- ing, the need for a tropism the outside of a CD4 cell, or on concomitant medica- tors (except for Aptivus), test, and competition from and shuts down this point n AVERAGE WHOLESALE PRICE tion known to lower blood Stribild, Genvoya, Tybost, newer drugs have dimmed of entry for the virus. Most 300 mg tablets, pressure. Patients with car- Rescriptor, clarithromy- some of the initial enthusi- people are infected with 60 tablets: $1,874.44/ diovascular comorbidities cin, and itraconazole; 300 asm for this drug. Selzentry R5 virus initially, and then month could be at increased risk mg twice daily if taken appears to be synergistic over time, X4 and mixed of cardiovascular adverse with Aptivus, Viramune, with Trogarzo for people viruses may predominate. events triggered by postural Isentress, Tivicay, Triumeq, with extensive HIV drug Blocking R5 with Selzentry

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Trogarzo ibalizumab-uiyk (IBA) AI ENTRY/ATTACHMENT INHIBITOR: FOR PEOPLE LACKING SUFFICIENT TREATMENT OPTIONS; CD4 POST-ATTACHMENT INHIBITOR ▼ SEE ‘MORE INFORMATION SECTION’ BELOW n DOSE USED IN STUDIES • approved CD4 post-attach- DR. DAVID HARDY SAYS: Trogarzo was approved Administered once every two weeks via intravenous ment inhibitor ibalizumab.” by the FDA in March 2018 and is the first anti- infusion. Treatment begins with an IV loading (start- Ibalizumab is a shiny brand retroviral given exclusively as an intravenous (IV) infu- ing) dose of 2,000 mg, followed by an 800 mg IV new option, but it doesn’t sion. Trogarzo is the first monoclonal (synthetically infusion maintenance dose given every two weeks come without some rules. produced) antibody that prevents HIV from attaching thereafter. Must be taken in combination with another It is expensive because to the CD4+ receptor on the surface of CD4+ T cells. antiretroviral(s). the cost of the drug will be Due to this specific inhibition process, HIV cannot added to other expenses grab onto and get inside of a PLWH’s CD4+ T cells and The first infusion takes at least 30 minutes. If no such as the time at the infu- cause infection of that cell. A small but conclusive infusion-related adverse events occur, subsequent sion center and qualified study showed that Trogarzo significantly dropped viral infusions take 15 minutes. Doses may be administered individuals to administer loads in PLWH with highly drug-resistant HIV when every two weeks at an inpatient and/or outpatient setting, and handle the medica- the drug was infused by vein into these persons every including at-home infusion, if desired. All patients should tion, although there may be 2 to 4 weeks along with other antiretrovirals. The side be observed for 1 hour after completing first infusion. If an option for patients to effects of this monoclonal antibody treatment are no infusion-associated adverse reaction is noted, the post- receive their infusion at minimal and well tolerated. It is notable that in this infusion observation time can be reduced to 15 minutes. home. Non-adherence study, 43% (17 of 40) of PLWH also received fostemsa- Must be given with an optimized background regimen won’t be an option—people vir as one of the active agents in an optimized treat- (OBR). An OBR consists of the best antiretroviral therapy won’t be able to just show ment regimen. Also notable is the cost of Trogarzo; its that can be made for each patient based on the patterns up whenever they want or monthly wholesale acquisition cost (WAC) is $9,089, of HIV drug resistance in their virus. Dose modifications be late to appointments or $108,960 per year. of Trogarzo are not required when administered with any when going to an infusion other antiretroviral or any other treatments. center. It will be like chemo- ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: If a maintenance dose of Trogarzo is missed by 3 days therapy or dialysis. Patients 0 Ibalizumab is a new drug in the entry inhibi- or longer beyond the scheduled dosing day, a loading must be on time. tor drug class. The way it works is different from all dose (2,000 mg) should be administered as early as Trogarzo is new and the other antivirals. It blocks viral entry into cells possible. Then resume maintenance dosing (800 mg) works differently than any by attaching to a different domain on CD4 cells. every 14 days thereafter. other available HIV medica- Ibalizumab works against both CCR5 and CXCR4 virus. tion. Ibalizumab is the first It is not metabolized in the liver or eliminated by the HIV drug that is not taken kidneys. Ibalizumab is what is known as a humanized ➤ SEE PACKAGE INSERT for mechanism of action and every day. Still, because it monoclonal antibody. It is the first medication to treat more complete informa- pharmacokinetic profile, must be used with other HIV that is not taken daily. It must be used in combination on potential side drug-drug interactions are HIV medications, antivi- tion with other HIV medicines. This is what we know as effects and interactions. not expected. No drug ral treatment will still be a salvage therapy, meaning it is for people with multi- interaction studies have required to be taken daily. drug resistant HIV who cannot achieve undetectable n POTENTIAL SIDE EFFECTS been conducted with Ibalizumab is also the first levels of HIV. It is administrated by IV infusion. AND TOXICITY Trogarzo. Tell your provider HIV orphan drug—one that The most common adverse or pharmacist about all is produced for a relatively reactions observed in clini- medications, herbals, and small population of patients the first HIV medication metabolized in the liver nor cal studies were diarrhea supplements you are tak- (fewer than 200,000). It made from cells rather eliminated by the kidneys. (8%), dizziness (8%), nau- ing or thinking of taking, was produced for people than from chemicals. This No adequate human data sea (5%), and rash (5%). prescribed or not, as there with multi-drug resistant does not make ibalizumab are available to establish Additionally, selected lab are other drug interactions HIV, estimated to be fewer better, just different. All whether or not Trogarzo abnormalities noted to which are not listed here. than 40,000 in the U.S.; monoclonal antibodies (or poses a risk to pregnancy occur in at least 5% of stud- the company estimates mAbs, hence the last syl- outcomes. Monoclonal anti- ied patients were increased n MORE INFORMATION that there are fewer than lable of “ibalizumab”), are bodies such as ibalizumab bilirubin (greater than 2.6 Essentially, this drug’s 25,000. These are heav- made this way, including are transported across times ULN—upper limit niche is deep salvage ily treatment-experienced biologics used to treat the placenta as pregnancy of normal) (5%), increased therapy for heavily treat- people who have multi-drug rheumatoid arthritis and progresses; therefore, ibali- creatinine (greater than1.8 ment-experienced people resistance, and have there- psoriasis. Ibalizumab works zumab has the potential to times ULN or 1.5x baseline) with multi-drug resistance, fore, usually, limited treat- differently from any other be transmitted from the (10%), increased lipase along with an optimized ment options. Ibalizumab HIV drug currently on the mother to the developing (greater than 3 times ULN) background regimen (OBR). has been shown to work market. It binds to a domain fetus. The safety and effec- (5%), decreased leucocytes A key point is that people against highly drug-resistant (location) of the CD4 recep- tiveness of Trogarzo in pedi- (5%), and decreased neu- must still take other HIV virus, when combined with tor (in this case, domain atric patients have not been trophils (5%). Most (90%) medications that have an OBR. 2), blocking viral entry into established. of the adverse reactions some activity—there has Ibalizumab was studied the CD4 cell. Ibalizumab reported were mild or mod- to be at least one HIV in a relatively small (only works against both CCR5 n MANUFACTURER erate in severity. No formal drug to which their virus is 40 patients!) Phase 3 study. and CXCR4 virus, and TaiMed USA studies were conducted to sensitive included in their Individuals with advanced appears to be synergistic DISTRIBUTED BY examine the effects of either OBR. U.S. HIV treatment disease and limited treat- with all other classes of Theratechnologies Inc. renal or hepatic impairment guidelines list Trogarzo this ment options receiving antiretrovirals. Resistance theratech.com on the pharmacokinetics of way: “Patients with ongoing Trogarzo noted significant test results revealed no evi- trogarzo.com ibalizumab. Renal impair- detectable viremia [detect- improvements in viral load dence of cross-resistance ment is not anticipated to able viral load] who lack reduction and T cell increas- between Trogarzo and any n AVERAGE WHOLESALE PRICE impact the pharmacokinet- sufficient treatment options es. After the initial loading of the approved classes $2,724.00 per vial; ics of ibalizumab. to construct a fully suppres- dose, 83% of participants of HIV drugs. Ibalizumab 10 vials for loading dose sive regimen [get to unde- achieved a clinically signifi- is widely considered to and two vials for continu- n POTENTIAL DRUG INTERACTIONS tectable viral load] may be cant decrease in viral load. be an HIV entry inhibitor ing dose (every two weeks) Based on Trogarzo’s candidates for the recently As a biologic, IBA is medication. IBA is neither

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INVESTIGATIONAL DRUG AT PRESS TIME.

fostemsavir (FTR)

PHOTO UNAVAILABLE AI ENTRY/ATTACHMENT INHIBITOR: DHHS RECOMMENDATION gp120 ATTACHMENT INHIBITOR ● NOT YET ESTABLISHED n STANDARD DOSE • all medications, herbals, DR. DAVID HARDY SAYS: Fostemsavir is a pro- In clinical trials, the investigational dose taken forward and supplements you are drug that is metabolized to the active com- for further study was 600 mg, sometimes once daily taking or thinking of taking, pound temsavir, an attachment inhibitor that binds to and sometimes twice daily. Doses were taken after prescribed or not, as there glycoprotein 120 (gp120) on the envelope of HIV’s sur- eating. Must be taken in combination with another are other drug interactions face. It works by locking HIV gp120 in a conformation- antiretroviral(s). which are not listed here. al state that inhibits the necessary binding between the virus and the CD4+ protein on human T cells, and Recommended for heavily treatment-experienced n MORE INFORMATION prevents viral attachment and entry into these cells. patients with history of 3-class antiretroviral resistance May be FDA approved this Because of its unique mechanism of action, there is in addition to an optimized background regimen of other year. Fostemsavir is the no known cross-resistance with other classes of anti- active antiretroviral drugs. Not studied in treatment-naïve first HIV drug of its type to retrovirals which may help PLWH whose viruses have patients at this time. No data in pregnant women or get this far in development. become resistant to most other medications. While pediatric patients under age 18 years. It’s a gp120 attachment the BRIGHTE study data has been submitted to the Take missed dose as soon as possible, unless it is inhibitor. (That’s under the FDA for review, fostemsavir’s approval has been closer in time to your next dose. Do not double up on drug class of HIV entry delayed due to manufacturing limitations. It is expect- your next dose. inhibitors.) Watch a video ed that fostemsavir will be approved and available in of its mechanism of action 2019. It is given as a tablet twice daily along with other at youtu.be/WnreXE-TVi8. antiretrovirals. The BRIGHTE study (NCT02362503) is ➤ SEE PACKAGE INSERT percent of study partici- Fostemsavir works on the a two-cohort (randomized and open-label), Phase 3 when available for more pants overall discontinued gp120 protein that lays clinical trial evaluating the safety and efficacy of fos- complete information the study due to an adverse on the surface of human temsavir in 371 heavily treatment-experienced PLWH. on potential side effects event. immune cells. It’s a neces- All had documented resistance, intolerability, and/or and interactions. sary part of getting the virus contraindication to all antiretrovirals in at least four of n POTENTIAL DRUG INTERACTIONS to enter the cell. Fostemsavir the six available ART classes. PLWH in the randomized n POTENTIAL SIDE EFFECTS New interactions continue prevents attachment to the cohort had to have one, but no more than two, fully AND TOXICITY to be discovered after drug CD4 immune cell by bind- active antiretroviral classes remaining at baseline, but In the Phase 3 BRIGHTE approval. Dose modifica- ing to the CD4 receptor were unable to construct an effective regimen from study results out to one year tion of fostemsavir is not binding sites on gp120 their remaining antiretrovirals. These PLWH were ran- (48 weeks), a third of par- required when co-admin- on the virus. This causes domized 3:1 to add blinded fostemsavir or blinded pla- ticipants experienced one or istering with tenofovir DF, the virus to accumulate in cebo (n=272) to their current failing regimen for eight more serious adverse event ritonavir-boosted atazanavir, extracellular space and is days of functional monotherapy. Patients without any (SAE), mostly infections (of ritonavir-boosted darunavir subsequently removed by remaining fully active approved antiretrovirals (n=99) which pneumonia was most with or without etravirine, the body’s immune system. were assigned to the open-label cohort and received common). Three percent of etravirine alone, ritona- Very cool. Fostemsavir is fostemsavir plus other optimized antiretrovirals. The the SAEs were related to vir alone, or raltegravir + likely to be approved as an primary endpoint of the study was mean change in fostemsavir. A high rate of tenofovir DF. Dose modifi- oral twice-daily drug, mak- viral load between Day 1 and Day 8 for the random- SAEs in the study popula- cation is also not required ing it unlikely to be used in ized cohort. After the 8-day blinded period, all patients tion is not unexpected, given when co-administering with treatment-naïve individuals. in the randomized cohort received open-label fostem- the heavily HIV treatment- rifabutin (with or without The drug is designed to be savir plus an optimized ART regimen. By Day 8, those experienced background ritonavir). It is not recom- used in HIV treatment-expe- PLWH who received fostemsavir saw their viral loads of participants, and likely mended to co-administer rienced people, who typi- drop by 0.8 log10, or about 6.5-fold, compared with a their advanced disease. In with rifampin due to sig- cally have fewer options for 0.2 log10 drop among those who received placebo, a week 24 BRIGHTE safety nificantly reduced levels of HIV treatment than those thus confirming fostemsavir’s anti-HIV activity in high- report, 91% of participants fostemsavir. Based on fos- just beginning antiretroviral ly treatment-experienced PLWH. After 48 weeks, 62% had experienced at least temsavir’s metabolism, a therapy. An option for treat- of PLWH in the randomized group had undetectable one adverse event, mostly theoretical interaction likely ment-experienced individu- viral loads (less than 40 copies/mL) and 86% had viral Grade 1 or 2 (mild to mod- exists with statins (drugs als is a good thing. “Even in loads below 400 copies/mL. Among PLWH in the ini- erate). Grade 2 to 4 adverse used to treat high choles- the era of modern HAART tial open-label group, 48% had viral loads less than 40 events (moderate to serious) terol). This may require a [highly active antiretrovi- copies/mL and 55% had viral loads less than 400 cop- occurring in a total 18% of dose reduction or adjust- ral therapy], antiretroviral ies/mL. PLWH in the randomized group experienced participants included nau- ment of certain statins (ARV) failure and resistance an average rise in CD4+ T cells of 139/mm3 , while sea (4%), diarrhea (2%), when co-administered is still a problem worldwide,” those in the initial open-label group gained an average headache (2%), vomiting with fostemsavir. No dose wrote HIV specialist Dr. of 64 CD4+ T cells/mm3 . (2%), fatigue (1%), and modification necessary Pedro Cahn and colleagues asthenia (muscle weakness) when co-administered with in Current Opinion in HIV ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: (1%). Remember, most of methadone or buprenor- and AIDS published last 0 Fostemsavir is developed to be used in PLWH the participants were also phine. Fostemsavir could July. Dr. Cahn worked on with multi-drug resistance. Fostemsavir is a prodrug. taking at least one other affect oral contraceptive fostemsavir research. See When the drug is taken, it metabolizes to the active new drug. Seventeen par- concentrations, especially more data online. compound, temsavir, which inhibits the binding of HIV ticipants (5%) died, due to those containing ethinyl to CD4+ T cells through blocking the HIV gp120 AIDS-related causes or IRIS estradiol. If a booster is not n MANUFACTURER receptor. Since this is a highly conserved protein (immune reconstitution given in the regimen with ViiV Healthcare between HIV strains, fostemsavir has a high genetic inflammatory syndrome, in fostemsavir, it may be co- viivhealthcare.com barrier to resistance, and its novel method of action which the body begins to administered with a com- (877) 844-8872 provides an alternative option for patients with highly wake up “sleeping” illness- bined oral contraceptive resistant viral HIV strains. es as the immune system containing norethindrone n AVERAGE WHOLESALE PRICE improves). Again, this is and 30 mcg or less of ethi- Not yet established. not unexpected in patients nyl estradiol. Tell your pro- with advanced disease. Six vider or pharmacist about positivelyaware.com/fostemsavir POSITIVELY AWARE M A R CH + A P RIL 201 9 63 2019 POSITIVELY AWARE HIV DRUG GUIDE

Egrifta tesamorelin for injection NON- INJECTABLE FOR TREATING HIV-RELATED HIV EXCESS BELLY FAT (LIPOHYPERTROPHY) n STANDARD DOSE • who have pituitary gland compared to those on place- particles. Once mixed, the 2 mg via subcutaneous (under the skin) injection once tumor(s), pituitary gland bo. Despite initial thoughts vial should be rolled gently, daily in the abdomen, rotating injection sites and surgery, or other pituitary that Egrifta may have sig- not shaken, between the avoiding scar tissue, bruises, and the navel (see step- gland problems; active nificant drug-drug interac- hands for 30 seconds to by-step video at egrifta.com and this page for more cancer; hypersensitivity to tions with medications that ensure reconstitution into a information). either tesamorelin and/or use CYP450 (an enzyme in clear, colorless solution and mannitol; or who are preg- the liver) for metabolism, a administered right away. If nant. Egrifta should be used study in healthy volunteers not used immediately, the A potential complication of (GRF), which stimulates the with caution in patients proved otherwise. However, reconstituted Egrifta should HIV, antiretroviral therapy, pituitary gland to produce who have a history of it has not been studied with be discarded. or both may be changes and secrete the body’s own non-malignant neoplasms medications that use other in the distribution of adi- growth hormone. Egrifta (abnormal growth of tissue enzymes in the liver; there- n CAP & PAP INFO pose tissue (fat), otherwise reduces VAT while preserv- such as a tumor), a history fore, response to medica- Co-pay covers up to known as lipodystrophy; ing subcutaneous fat. The of treated and stable malig- tions that are metabolized $6,000 per year. If previous reports of preva- effect of this agent appears nancies, elevated insulin- through the liver should be someone is having lence in the U.S. varied to be greatest within the like growth factor 1 (IGF-1), monitored for response and difficulty paying for Egrifta, widely, anywhere from first three to six months of fluid retention, diabetes, or adverse reactions. Long- there are several programs 2–60% of all HIV-positive initiation. pre-diabetes. term safety data is unknown. available through Thera patients. Abdominal lipo- Two Phase 3 clinical The most common side There have been previous patient support at (833) hypertrophy (a form of trials found that Egrifta effects include joint pain, reports of a theoretical 23-THERA (833-238- lipodystrophy) is the accu- significantly lowered VAT injection site reactions increased risk of cancer with 4372), Monday–Friday, mulation of excess visceral (up to 15–20% on average) (including redness, pain, elevated IGF-1 levels. Other 8 a.m.–8 p.m., EST or at adipose tissue (VAT)—deep at both 26 and 52 weeks. and itching), pain in legs long-term concerns include egrifta.com. belly fat surrounding the Egrifta may also lower tri- and arms, swelling in legs, potential development of liver, stomach, and other glycerides (a type of choles- muscle soreness, tingling, retinopathy in patients with n MANUFACTURER abdominal organs. Egrifta terol). Adverse events were numbness and prickling, diabetes. Each dose neces- Theratechnologies, Inc. is the first, and only, FDA more commonly seen in the nausea, vomiting, rash, and sitates mixing 1-mg vials egrifta.com approved medication to groups given Egrifta than itchiness. Other warnings (requiring refrigeration) of Thera Patient Support: reduce VAT. This is differ- in those receiving place- include hypersensitivity Egrifta with 2.2 mL of ster- (833) 23-THERA ent from subcutaneous fat. bos. It is important to note reactions and acute critical ile water for injection (vial (833-238-4372) Unlike growth hormone that excess VAT returns illness. In the Phase 3 clini- stored at room temperature). therapatientsupport.com products, Egrifta is an once Egrifta is discontin- cal studies, patients receiv- Do not use an unopened analogue of human growth ued. Egrifta should not be ing Egrifta had a higher vial if the solution is colored, n AVERAGE WHOLESALE PRICE hormone-releasing factor administered to patients risk of developing diabetes cloudy, or contains visible $5,850.00/month

Mytesi crofelemer NON- ANTI-DIARRHEAL APPROVED FOR USE IN THOSE HIV WITH HIV/AIDS AND ON ANTIRETROVIRAL THERAPY n STANDARD DOSE achieve the optimal effect. cough, flatulence (gas), and and loperamide. Patients One 125 mg delayed-release• tablet taken twice a day, Mytesi appears to work increased bilirubin. Based should be informed that the with or without food. The tablet should be swallowed best in those who have tried on animal data, Mytesi may benefits of Mytesi are not whole and not crushed or chewed. and failed non-prescription cause fetal harm. Mytesi immediate, possibly taking anti-diarrheals, have had has not been studied in about four weeks, and if an diarrhea for more than patients younger than 18 inadequate response is seen Mytesi (crofelemer) is At study entry, patients two years, have more than years old. Its usefulness in after three months, Mytesi the first, and only, anti- experienced an average of two watery bowel move- pediatrics is unknown and should be discontinued. diarrheal indicated for the approximately 20 watery ments per day, and whose use in this population can- symptomatic relief of non- stools per week. To be con- bowel movements tend to not be recommended at this CAP & PAP INFO infectious diarrhea in adult sidered a responder, watery be “pourable” (not clumpy). time. Co-pay program: patients with HIV/AIDS stools had to be decreased Mytesi was less effective in There were no signifi- (877) 336-4397 on antiretroviral therapy. to two or fewer per week, African Americans in this cant drug interactions in Pay no more than $25, Currently, what is typically which occurred in 18% of clinical study. participants in the clinical maximum benefit of $100 recommended is for the Mytesi-treated patients An infectious cause study. There was little or no on each prescription. patient to take medication(s) vs. 8% of placebo-treated should be ruled out prior change in CD4 counts and PAP: (888) 527-6276; with food and/or use patients at 4 weeks. In an to initiating Mytesi. In the viral load throughout the mytesi.com Imodium (loperamide) for open label extension phase placebo-controlled part of study. symptomatic diarrhea. of the study, about 50% of the study, side effects were In a review article in MANUFACTURER Mytesi approval was the patients reported two comparable to placebo. The Expert Review of Clinical Napo Pharmaceuticals based on a randomized, or fewer watery stools per most commonly reported Pharmacology published in mytesi.com placebo-controlled study of week at 3 months, an effect side effect was upper respi- 2015 by Castro et al., the (844) 722-8256 374 HIV-positive patients which was maintained until ratory tract infection (Mytesi, use of Mytesi is recommend- who had about 3 watery study end at 6 months. 3.8% of patients vs. placebo, ed as a reasonable choice in AVERAGE WHOLESALE PRICE stools per day and were These findings suggest that 2.9%). Other reported side patients not responding to $802.22/60 tablets on anti-HIV medicines. it may take some time to effects included bronchitis, over-the-counter psyllium

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Serostim somatropin for injection NON- INJECTABLE HUMAN GROWTH HORMONE USED FOR HIV TREATING HIV-ASSOCIATED WASTING IN THOSE ON ART n STANDARD DOSE • of diabetes, sometimes injuries, severe breathing there are several programs 0.1 mg/kg via subcutaneous (under the skin) injection, reversible upon stopping problems, certain eye dis- that may be able to assist which may be in the thigh, upper arm, abdomen, or but- Serostim), nausea, and eases related to diabetes, or the patient with acquiring tock once daily at bedtime (up to 6 mg), rotating injec- fatigue. More rarely, poten- after critical illness due to it. These programs include tion sites and avoiding scar tissue, bruises, and the tial side effects include complications of abdominal EMD Serono Secured navel. It is available in 4 mg, 5 mg, and 6 mg vials. The pancreatitis (watch for per- or open heart surgery. Distribution Program, the multi-use 4 mg vial is reconstituted with bacteriostatic sistent severe abdominal Based on how the drug is AXIS Center, the Serostim (containing a biological or chemical agent that stops pain) and intracranial hyper- broken down in your body, Patient Assistance Program bacteria from reproducing) water for injection and may tension (rise in pressure in there are some potential (PAP) or the Co-Pay be refrigerated for up to 14 days after reconstitution. the skull, with visual chang- drug-drug interactions, Assistance Program (CAP). The single-use 5 mg and 6 mg vials are reconstituted es, headache, nausea, or though no formal drug stud- To find out more about with sterile water for injection and must be used imme- vomiting). Serostim should ies have been conducted. these programs, call (877) diately; after administering the dose, any unused por- be avoided in patients These theoretically poten- 714 -2947. tion should be discarded. Some loss of the dose can be who are acutely ill, have tial interactions include This year, the co-pay expected (approximately 10%). Inject the water into the an active cancer, or have patients on glucocorticoid card is frontloaded. $0 ini- vial aiming for the glass wall. The vial should be swirled diabetic retinopathy (dam- (such as prednisone) ther- tial fill (rebate form provided gently in a circular motion until solution is completely age to one or both retinas). apy and may require an if you need to pay up front dissolved; it must be clear and colorless. Do not shake. Since HIV-positive patients increased prednisone dose. and are eligible), and up to Do not inject if solution is cloudy or contains particles. may have an increased risk Others may include medi- $1,500 for each additional of developing new tumors, cations that are metabo- monthly fill, not to exceed including from birthmarks lized through the CYP450 $18,000/year. PAP also Serostim is recombinant prescribed Serostim. or other moles, risks versus enzyme in your liver (like available if you qualify. Call (made in a lab) human Most common potential benefits of starting Serostim some antiretrovirals, cho- AXIS Center (877) 714- growth hormone for treat- side effects include swell- should always be dis- lesterol medications, or AXIS (2947). ment of HIV wasting (unin- ing (especially of the hands cussed with your provider. anticonvulsants); or medi- Go to serostim.com tentional loss of weight) or and feet), muscle pain, joint Additionally, patients with cations like oral estrogen, for additional information. cachexia (general ill health pain, numbness, and pain known malignancies should insulin, or oral diabetes resulting from emaciation), in extremities (the ends of be carefully monitored, drugs. Be sure to tell your n MANUFACTURER decreased lean body mass limbs, especially the hands because Serostim may provider, pharmacist, and/ EMD Serono (muscle), and loss of physi- and feet), carpal tunnel cause increased growth or or other providers about serostim.com cal endurance. Loss of mus- syndrome (requiring discon- malignant changes. all of the medications you (877) 714-AXIS (2947) cle can be difficult to notice tinuation if unresolved by Rotate injection sites to are taking, including herbs, or diagnose. Serostim has decreasing the number of avoid injection site reac- supplements, and over-the- n AWP been shown to increase doses), injection site reactions. An injection training counter (OTC) products, 6 mg: 7 injections (usually HIV replication in the test tions (pain, numbness, red- program is available; see prescribed or not. a one week supply) tube; therefore, patients ness, or swelling), increased the website or call the toll- $4,375.43 must be taking anti-HIV blood fat (triglycerides) free number. Do not use n CAP & PAP INFO therapy, known as HAART and blood sugar (including while experiencing cancer If someone is having dif- (or cART), in order to be new or worsening cases or cancer treatment, serious ficulty paying for Serostim,

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Truvada for PrEP emtricitabine/tenofovir DF (FTC/TDF) PrEP PrEP (PRE-EXPOSURE CDC RECOMMENDED PROPHYLAXIS) ★ FOR PREVENTION OF HIV n STANDARD DOSE • risk depends on the situa- drug approved for PrEP. use PrEP as their only For HIV-negative adults and adolescents weighing at tion—including where you There are many consid- prevention method, it was least 77 pounds (35 kg), one tablet once daily, without live or how much money erations regarding Truvada studied and approved as regard to food. The tablet contains 200 mg emtric- your friends have or some for PrEP. Proper use is part of a more comprehen- itabine and 300 mg tenofovir disoproxil fumarate. such. Stigma—not sex—is crucial. It is vital that sive HIV prevention strat- the real shame. Other prob- people test HIV-negative egy that includes the use Take a missed dose as soon as possible, unless it is lems include not knowing right before being given a of condoms and risk reduc- closer to the time of your next dose. Do not double up on about PrEP and inability to prescription (the label says tion counseling. That said, your next dose. Truvada should not be used for prevention perceive a need for it (not “immediately,” the CDC says the CDC has changed the if eCrCl or eGFR (measures of kidney function) is less realizing one may be vul- within 7 days). Patients definition of protected sex than 60 mL/min. nerable at all). Altogether, should also be re-tested to include sex without con- even doctors continue to for HIV infection at least doms, given new modalities avoid prescribing PrEP. every three months while such as PrEP. Although ➤ SEE THE INDIVIDUAL provider before discontinu- Although PrEP should taking Truvada for PrEP. consistent condom use is DRUGS CONTAINED IN ing. In studies, there were become medically routine, People who are already an important part of a pre- TRUVADA: Viread and cases of people who had like HIV tests for pregnant unknowingly HIV infected vention plan for all people Emtriva unidentified HIV infection women, until it is, we’ll when starting PrEP risk prescribed PrEP, lack of use ➤ SEE PACKAGE INSERT for when starting Truvada for tell you again: seeing an developing drug-resistant of a barrier protection is not more complete informa- PrEP and subsequently HIV specialist is the best virus because Truvada a reason to withhold PrEP. tion on potential side developed drug resistance. way to obtain PrEP. They alone is not adequate for On the contrary, the PrEP effects and interactions. A negative HIV test must get it. It’s not about being the treatment of HIV. Drug label lists people who are be confirmed immediately a whore. And better yet, resistance can only occur unwilling or unable to use n POTENTIAL SIDE EFFECTS prior to starting Truvada for they care. Fortunately, new in HIV-positive individuals. condoms as at-risk candi- AND TOXICITY PrEP. Truvada alone is not avenues for PrEP—many Truvada for PrEP should dates for whom the drug No new serious side effects a complete regimen to treat without HIV specialty—are not be given to people with is indicated. PrEP does not were seen when Truvada HIV. Continuing only with opening up: pharmacist-led symptoms of recent (acute) protect against other sexu- was studied for HIV preven- Truvada after acquiring HIV PrEP clinics, tele-PrEP (via infection, such as fever, ally transmitted infections tion in clinical trials. Some may lead to drug resistance video consultation), use of fatigue, sweating a lot (STDs) including hepatitis C patients may experience and limit future antiviral ERs and STD clinics, and (especially at night), rash, or against pregnancy. nausea, headache, stomach options. Truvada contains so on. As for “just use a vomiting, diarrhea, joint or pain, or weight loss. Risk lactose, which can cause condom,” there are many muscle aches, headache, Other screening and compensation (when people some abdominal discomfort, reasons why condoms are sore throat, or enlarged monitoring requirements put themselves at greater especially in patients sensi- not enough. So can we lymph nodes (especially include measuring kidney risk for infection, such as tive to lactose. move on? in the neck or groin). PrEP function and checking for anonymous or multiple sex Truvada, a widely-used should not be started (or STIs and hepatitis B and partners, because they think n POTENTIAL DRUG INTERACTIONS medication for the treat- re-started) if any of these C, treatment for STIs, and PrEP will protect them) was Do not take with any other ment of HIV, was approved symptoms appear after a vaccination for HBV if not observed in clinical trials. HIV or HBV drugs when in July 2012 by the Food potential exposure to HIV warranted. The tenofovir DF (Viread) in used for PrEP. Avoid tak- and Drug Administration unless evaluated by a doc- Truvada is associated with ing Truvada with drugs (FDA) to reduce the risk tor and possibly re-tested Although a PrEP prescrip- long-term decreases in that negatively affect the of HIV infection in HIV- for HIV. People on PrEP tion can be given to a bone mineral density (BMD). kidneys, including chronic negative individuals ”at risk” who have these symptoms wide range of people, the BMD monitoring should be use or high doses of anti- for HIV acquisition (accord- after a potential exposure Truvada PrEP drug label considered in people who inflammatory drugs for pain ing to the drug label – in to HIV should let their pro- states that it is indicated have a history of bone like Advil or Motrin (ibupro- reality, people rarely realize vider know immediately. for those considered “at fracture due to a disease fen) and Aleve (naproxen). that they’re at risk for HIV risk” for infection. The label or are at risk for osteopenia Truvada for PreP can be at all). Although the drug Truvada for PrEP is not notes that people at risk or osteoporosis. Truvada used with the hepatitis C label specifies sexually- a “morning-after pill” or include those who engage can cause kidney toxici- drugs Daklinza, Harvoni, acquired infection, U.S. HIV a weekend medication. It in sexual activity in a high- ties. In prevention studies, Sovaldi, Olysio, Viekira guidelines also recommend must be taken every day prevalence area or social decreases in BMD and cre- Pak, or Zepatier. Monitor use for protecting against to be maximally effective. network and have one or atinine clearance or eGFR for tenofovir toxicities if infection through injection In studies, greater protec- more of the following: (a) (a marker of kidney func- used with Epclusa. Tell drug use (reducing the risk tion was seen with greater inconsistent or no condom tion) were rare, mild, and your provider or pharma- of HIV by more than 70%, adherence. Truvada for use, (b) diagnosis of sexu- reversible upon stopping cist about all medications, according to the CDC). This PrEP works if you take it ally transmitted infections Truvada. Tell your provider herbals, and supplements approach to HIV preven- as prescribed. On the other (STIs), (c) exchange of sex about pain in extremities, you are taking or thinking of tion is called pre-exposure hand, there have been good for commodities (money, persistent or worsening taking, prescribed or not. prophylaxis, or PrEP (“pro- results with using it around food, shelter, or drugs), (d) bone pain and fractures, phylaxis” means something the time of sex (kudos to use of illicit drugs or alco- with or without muscular n MORE INFORMATION that prevents disease, such the IPERGAY study)—the hol dependence, (e) his- pain or weakness, as well Let’s be clear: Truvada for as a condom or a vaccine). research continues. Unlike tory of incarceration, or (f) as any concerning changes PrEP is almost 100% effec- The U.S. Public Health HIV therapy, which is long- sexual partners of unknown in urinary habits as these tive in preventing HIV—this Service (USPHS) has term, PrEP may be used HIV status with any of the could be signs of kidney or is a done deal. Why aren’t issued updated guidelines just for periods of time above risk factors. U.S. bone problems. If Truvada more people using it to help for the use of Truvada for when HIV-negative indi- HIV treatment guidelines is discontinued abruptly in end the epidemic? Stigma PrEP. Go to cdc.gov/hiv/ viduals are most vulnerable state that, “Truvada has people with hepatitis B virus and lack of access to health pdf/risk/prep/cdc-hiv- to infection. been shown to be safe and (HBV), flare-up of hepatitis care continue to fuel HIV prep-guidelines-2017.pdf. effective at preventing HIV may occur—talk to your infections. Remember, Truvada is currently the only While some people may in healthy adults who meet

68 MARCH+APRIL 2019 POSITIVELY AWARE positivelyaware.com/truvada-for-prep 2019 POSITIVELY AWARE HIV DRUG GUIDE

recommended criteria in the also been studied in other vulnerable to HIV. Health DR. DAVID HARDY SAYS: Truvada was FDA following populations: MSM patient populations, includ- departments across the approved as the first antiretroviral for pre-expo- [men who have sex with ing younger single men and country are promoting sure prophylaxis (PrEP) for HIV in July 2012 based men], heterosexually active women, injection drug users, PrEP as part of a strategy upon a very robust package of placebo-controlled ran- men and women, and IV and women. In all the stud- to end the HIV epidemic. domized clinical trials among MSM and TGW (iPrEX drug users.” ies, the common theme In addition, prevention study); serodiscordant, heterosexual couples Individuals who have is that PrEP is effective if efforts are also focusing (Partners PrEP study); single, heterosexual couples used post-exposure prophy- you take it every day. Other on U=U (Undetectable (TDF-2 study); and male and female injection drug laxis (PEP) multiple times drugs are being studied for equals Untransmittable), users (Bangkok Tenofovir study). While its uptake was are also good candidates use as HIV PrEP, including promoting the awareness initially slow in the U.S., a significant increase in for PrEP because of their long-acting injection formu- that people living with HIV Truvada for PrEP prescriptions has been seen since continuing risk for HIV. PEP lations requiring only one who have undetectable viral 2016 with an estimated 220,000 to 250,000 persons is a course of HIV medica- injection every 4–8 weeks. loads do not transmit the receiving PrEP in the U.S. (PrEPWatch, August 2018; tions taken for 28 days after virus to sexual partners. Go prepwatch.org/country/united-states, accessed exposure to HIV to prevent Some providers not work- to preventionaccess.org. January 14, 2019). However, several reports from HIV infection; it must be started ing in HIV are still learn- Providers are reporting conferences have focused on the disproportionate as soon as possible but no ing about PrEP, and some widespread acceptance high uptake among white MSM but low uptake among later than 72 hours after continue to be reluctant to of PrEP prescriptions by black and Hispanic MSM, and cis-gender, heterosexu- exposure. prescribe it. Read the PDF insurers. Gilead Sciences al, and transgender women (natap.org/2018/CROI/ of the CDC brochure “Talk helps patients work with croi_196.htm). A report at the IAS 2018 conference Although pregnant women to Your Doctor about PrEP.” their insurance, including from the CDC, Emory University, and Gilead showed a were not enrolled in PrEP The brochure includes pre-authorizations, as well significant decline in newly diagnosed PLWH in areas studies, there is hope for resources for providers. HIV as provides free PrEP to of the U.S. where PrEP uptake was the highest (poz. PrEP to help serodiscordant specialists may be best for uninsured patients who com/article/rising-prep-use-associated-declining-hiv- couples (where one partner a PEP or PrEP prescrip- are eligible and co-pay diagnoses-united-states). Also, of note, the approval is positive and one is nega- tion, as they are familiar assistance up to $4,800 of Truvada for PrEP was extended to smaller and tive) conceive without trans- with the medications and a year; contact the patient (most likely) younger persons at-risk for HIV as the mitting the virus. Last year, more supportive of PrEP; assistance hotline at FDA approved the use of Truvada for PrEP in persons the DHHS perinatal HIV find providers at hivma.org (855) 330-5479, or go to weighing at least 35 kilograms or 77 pounds in May of guidelines added a section and aahivm.org, as well as gileadadvancingaccess.com. 2018. With the availability of the generic, near-equiva- on the use of PrEP and HIV pleaseprepme.org. HIV Patients may also need lent, and less costly Cimduo (tenfovir DF/lamivudine; therapy to prevent trans- specialists are generally to advocate on their own see that page), the use of this antiretroviral for PrEP is mission in sero-different in high demand, however, behalf; keeping good notes a growing possibility. Regulatory-wise and according couples trying to conceive; and advocates are looking of conversations and other to the FDA, Cimduo is not officially approved for PrEP, go to aidsinfo.nih.gov. The to make Truvada for PrEP communication is a good only for treatment of HIV. Will this distinction matter Bay Area Perinatal AIDS much more accessible. idea. Also, check out when it comes time to spend less money and increase Center (BAPAC) is leading There is also a complex prep4love.com. access to PrEP? the charge for safer concep- set of standards to use in tion options, including MSM, prescribing PrEP that may PrEP Facts: Rethinking ACTIVIST MOISÉS AGOSTO-ROSARIO SAYS: plus a new providers list at cause many providers to HIV Prevention and Sex is 0 PrEP is short for pre-exposure prophylaxis, pleaseprepme.org; go to turn away, including a call a closed Facebook group which means protecting yourself from exposure hiveonline.org. for safer sex counseling. for people interested in to the HIV virus. Truvada is an HIV drug that has According to the World Requirements for a PrEP or currently on PrEP, and proven to reduce the risk of getting infected with HIV Health Organization, it prescription can be burden- their allies. Demonstration through sex. It is prescribed to be taken once a day, takes Truvada for PrEP 7 some. Truvada for PrEP projects providing free every day. Adherence is very important for PrEP to days to reach protective has a Risk Evaluation and PrEP to study its use in the work. You have to be tested before using Truvada for levels, whether exposure is Mitigation Strategy (REMS) real world can be found at PrEP and every three months see your health care rectal or vaginal. The CDC program which providers PrEPWatch.org from AVAC provider who will test you for HIV and other sexually notes time to steady state, can access to ensure safe and projectinform.org/prep. transmitted diseases (STDs). Truvada for PrEP does or maximum intracellular prescribing. The National Providers can use V107 as a not reduce the risk for contracting STDs; that’s why concentrations of tenofovir Alliance of State and medical billing code for PrEP it is strongly recommended to practice safer sex diphospate (TFV-DP), of 7 Territorial AIDS Directors (exposure to infectious dis- practices even if you take Truvada for PrEP. Truvada days for the rectal tract and (NASTAD) developed a ease, including HIV). can cause serious adverse events like kidney damage about 20 days for vaginal guide to help providers bill and bone density loss. You should be monitored for tissue. Protective levels, for PrEP services available Other information sources: both. Liver damage might occur, so it is important to however, are reached much at nastad.org/resource/ n cdc.gov/hiv/basics/prep check your liver enzymes. earlier, based on pharmaco- billing-coding-guide-hiv- n nccc.ucsf.edu/ kinetic (PK) models. prevention. Two excellent clinical-resources/ The two studies that websites for finding a PrEP pep-resources/prep interventions for both HIV n MANUFACTURER led to Truvada’s approval provider are preplocator. n whatisprep.org prevention and treatment Gilead Sciences, Inc. for PrEP, iPrEx (in high- org and aidsvu.org. All you n truvadapreprems.com has led to unprecedented gilead.com risk MSM and transgender need to do is enter your ZIP n hivinsite.com optimism about the pros- truvada.com women) and Partners PrEP code, and a list of providers pect of ending AIDS.” cdc.gov/hiv/basics/prep.html (in serodiscordant couples, who prescribe Truvada for Robert Grant, MD, prin- (800) GILEAD-5 most of them heterosexu- PrEP will appear. cipal investigator for the Read POSITIVELY AWARE’s (445-3235) al), showed efficacy rates Greater PrEP accep- iPrEx study, wrote in an special issues on PrEP: between 90%–92% when tance and use, however, article for POSITIVELY positivelyaware.com/ n AVERAGE WHOLESALE PRICE participants take their meds. appears to be increasing AWARE, “The combination issues/prep-issue- $2,010.95/month PrEP with Truvada has among communities most of highly active antiretroviral summer-2015. positivelyaware.com/truvada-for-prep POSITIVELY AWARE MARCH+APRIL 2019 69 2019 POSITIVELY AWARE HIV DRUG GUIDE HIV LIFE CYCLE An ensemble cast How different drug classes play their part—and a look at some of the new players

HIV (HUMAN IMMUNODEFICIENCY VIRUS) UB-421 (CD4 receptor) Monoclonal VRC01 (CD4 receptor) gp120 1 capsid antibodies (mAb) 3BNC117 and 10-1074 Entry inhibitors Binding gp41 PGDM1400 and PGT121 fostemsavir 10E8.4/iMab combinectin CD4 RECEPTOR PRO-140 (CCR5 recep.) CCR5 CORECEPTOR 2 Fusion NRTIs (nukes) EFdA (MK-8591) GS-9131 HIV RNA

NNRTIs CD4 cell (non-nukes) elsufavirine 3 CELL rilpivirine LA Reverse NUCLEUS transcripton HIV DNA 5 New viral 4 material Integration INSTIs 6 cabotegravir Maturation cabotegravir LA and budding

NEW HIV

Protease inhibitor GS-PS1 Capsid inhibitor GS-CA1 All of the compounds listed Maturation above are investigational; read about some of them in inhibitor “Coming Attractions” on the GSK3640254 following page. >>

STAGES OF THE HIV LIFE CYCLE

1. BINDING 2. FUSION 3. REVERSE 4. INTEGRATION 5. REPLICATION 6. MATURATION HIV attaches to HIV enters a TRANSCRIPTION Integrase enables Protease cuts AND BUDDING a CD4 cell. CD4 cell and Reverse HIV to join the and reassembles Each cell produces HIV proteins and transcriptase cell DNA. new HIV. hundreds of new enzymes are makes double virions. released strand HIV. into the cell.

SOURCE: HIV i-Base (www.i-Base.info)

70 MARCH + APRIL 2019 | POSITIVELY AWARE 2019 POSITIVELY AWARE HIV DRUG GUIDE WHAT’S NEXT Coming attractions A sneak peak at some of the new drugs coming soon

COMPLETED PHASE 3 PHASE 3 PHASE 1–2 SELECTED PRE-CLINICAL STUDY OR SUBMITTED COMPOUNDS NOT FOR APPROVAL cabotegravir MK-8591 (EFdA) IN HUMAN STUDIES Oral formulation of an inte- A new NRTI, highly potent, dolutegravir/3TC grase inhibitor mainly used low dose, active against NRTI Combinectin Single-tablet regimen com- for lead-in dose before long- resistance. Long half-life, (GSK3732394) prised of an INSTI and an NRTI. acting formulation. From ViiV. potential as oral (weekly dose) A gp41 / CD4 entry inhibitor. Phase 3 Gemini studies as and implant (annual implant Combined adnectin/fusion initial ART complete; TANGO cabotegravir LA/rilpivirine LA for PrEP). From Merck. inhibitor that stops viral entry switch study ongoing; regula- An INSTI/NNRTI injection by targeting multiple sites tory decision expected third with very long half-life— MK-8591/3TC/doravirine of action; potential for self- quarter of 2019. From ViiV. detectable after more than Fixed-dose combination of an administered once-weekly SEE DRUG PAGE IN THIS GUIDE. one year following single NNRTI + 2 NRTIs. Fixed-dose injections. From ViiV. injection. Studied as both combination with NNRTI fostemsavir (GSK3684934) treatment with rilpivirine doravirine plus generic 3TC GS-PS1 An ap120 attachment inhibi- CAB LAstudied as both treat- and new NRTI MK-8591 New once-daily unboosted tor. 48-week results from the ment with rilpivirine LA and (EFdA). From Merck. protease inhibitor; high Phase 3 BRIGHTE study in prevention as single INSTI potency, long half-life, poten- heavily treatment-experi- injection. From ViiV. GS-9131 tial for fxed-dose combina- enced with extensive drug SEE DRUG PAGE IN THIS GUIDE. A new NRTI active against tion single-tablet regimen. resistance; not yet submitted. NRTI resistance. Synergy From Gilead. From ViiV. PRO 140 reported with AZT, FTC, SEE DRUG PAGE IN THIS GUIDE. Monoclonal antibody CCR5 abacavir, efavirenz, bictegravir, GS-CA1 target. Once-weekly (350 mg) dolutegravir and lopinavir; Early stage for a new drug subcutaneous injection being additive activity with TDF class with activity at mul- studied in addition to ART for and TAF. Will be co-formulated tiple stages of viral lifecycle. multi-drug resistance and as with other Gilead drugs. Subcutaneous injection with monotherapy maintenance Phase 2 dose-fnding study in monthly or less frequent dos- therapy (without ART). Ugandan women. From Gilead. ing. From Gilead. From CytoDyn. GSK3640254 UB-421 A maturation inhibitor ABBREVIATIONS Monoclonal antibody CD4 acquired by ViiV from BMS. 3TC: lamivudine binding. Infusion dosed either AZT: zidovudine weekly or every two weeks 3BNC117 and 10-1074 FDC: fxed-dose combination as alternative to ART during Monoclonal antibodies. FTC: emtricitabine INSTI: integrase inhibitor treatment interruption. From Phase 1 open-label dose- mAb: monoclonal antibody United BioPharma. ranging studies include NNRTI: non-nucleoside studying these two anti- reverse transcriptase ADAPTED FROM bodies in HIV-positive and HIV Pipeline 2018: New Drugs inhibitor in Development, published by HIV-negative participants. NRTI: nucleoside reverse HIV i-Base, July 2018. For the Both also have longer-acting transcriptase inhibitor full report, go to http://i-base. (LA) formulations. From PI: protease inhibitor info/htb/34488. Rockefeller University. STR: single-tablet regimen TAF: tenofovir alafenamide TDF: tenofovir disoproxil PGDM1400 and PGT121 fumarate Another dual monoclonal ,11111111, antibody combination in a 111111I ,,1 Phase 1 study with the potential for both treatment and prevention. From the Ragon ,,,,1 Institute and IAVI. I ',,

POSITIVELY AWARE | MARCH + APRIL 2019 71 POSITIVELY AGING Positively Aging: BEGINNINGS New collaboration focuses on practical solutions for long-term survivors and older adults living with HIV

BY JEFF BERRY

Launched this year, Positively Aging is a new collaboration Health). In addition, the program between The Reunion Project and TPAN, the publisher of will incorporate group social activities to address the isolation known POSITIVELY AWARE. This joint venture seeks to strengthen to impede access to care for older an already-existing national network of long-term survivors adults. We need and create a new program in Chicago for older adults living Nationally, Positively Aging to improve with HIV, all the while elevating all our stories through will enable The Reunion Project to expand its outreach to and the quality profles, opinion pieces, and interviews in this new regular engagement with long-term sur- of life of column appearing in PA. vivors and other older individuals people living afected by HIV. In cities across with HIV Nationally, over 50% of people The Positively Aging collabora- the country, The Reunion Project living with HIV (PLWH) are over tion seeks to address some of will expand its schedule of local over age 50, the age of 50. But in Chicago, these issues. In Chicago, TPAN town halls to deliver vital access to and achieve where TPAN provides direct ser- will implement Positively Aging peer support and education. The health equity vices to the community, over 73% through the delivery of services tai- Reunion Project will also expand for all groups of PLWH are over 50. People are lored to the needs of older adults. its online and digital presence. living longer, and that’s a good Comprehensive mental health When I was diagnosed with HIV of people thing—it means we’re doing our services and case management in 1989, survival was not guaran- living with part to get people tested, into care, will be integrated with access teed. Treatments were suboptimal, the virus. and keeping them there. Getting to on-site primary medical care and I had no reason to think that them on efective treatment to (provided by TPAN’s existing on- I would make it while my friends keep their virus suppressed, and site collaborator, Howard Brown were all dying around me. Little did working to prevent transmission I know that I would be here today, from happening in the frst place. living, thriving, and aging with HIV But we can do better. We need some 30 years later. Programs to improve the quality of life of such as Positively Aging, and PLWH over 50, and achieve other collaborations and health equity for all networks of PLWH, are fnally groups of people beginning to emerge to address living with the virus. the unique challenges We need to ensure facing people living access to mental and aging with HIV. health services I’m grateful to be a for PLWH over part of them, and 50 that are blessed to work in a better targeted community that values and designed to the lives of all people address issues living, and aging, such as trauma, with HIV. PTSD, isolation, Putting hopes and depression. and dreams into We also need reality, creating real- to make sure world solutions, so that people that mental health can age positively—Positively providers are sensitive Aging. Tell us your plan for to the unique issues aging positively with HIV, and afecting older adults we might just share it here.

living with HIV. Email us at [email protected]. VENCAVOLRAB -ISTOCK

72 MARCH + APRIL 2019 | POSITIVELY AWARE EAT. DRINK. GIVE.

~ DIN ING DU T f.i:\ L~~:Stoeare ~ FDR LIFE '::9

DINING OUT FOR LIFE CHICAGO | APRIL 25, 2019 Help TPAN deliver compassionate care and health services to Chicagoans living with and affected by HIV. For details, go to tpan.com/diningout

Dining Out For Life is an international event involving the generous participation of restaurants, volunteers, corporate sponsors, and dining patrons in more than 60 cities—raising funds to support local lifesaving HIV/AIDS services. In Chicago, TPAN is the producer and benefciary of Dining Out For Life. To participate in a city near you, go to diningoutforlife.com. +

POSITIVELY AWARE LIVE LIFE POSITIVELY AWARE. IN PRINT. ONLINE. IN HAND.

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