HIV Prep – the Basics

HIV PrEP – The Basics

MADALENE MANDAP, PHARMD, BCPS , INTEGRATED PHARMACIST

TIFFANY MA, PHARMD, PGY1 PHARMACY PRACTICE RESIDENT

SOUTHCENTRAL FOUNDATION Pharmacist: 1. Identify appropriate indications and contraindications of HIV PrEP 2. Design an appropriate monitoring plan for HIV PrEP Learning 3. Compare and contrast HIV PrEP options

Objectives Pharmacy Technician: 1. Identify appropriate indications and contraindications of HIV PrEP 2. Recognize the medications indicated for HIV PrEP 3. List common side effects of HIV PrEP medications

PrEP = Pre-Exposure Prophylaxis Disclosures . We have nothing to disclose Pre-Assessment 1 AB is a 51-year-old transgender woman interested in starting HIV PrEP. She has the following: a) Recent HIV negative test b) Inconsistent condom use with partners of unknown HIV status, including PWID c) Treated for syphilis 3 months ago d) Has Hepatitis B infection e) CrCl = 28 ml/min Question: What of the above are indications or contraindications to HIV PrEP?

Pre-Assessment 2 CD is a 22-year-old cisgender MSM (man who has sex with men) who started HIV PrEP 2 weeks ago. He believes he is having side effects. Which of the following are commonly reported side effects to PrEP medication? a) Nausea b) Abdominal pain c) Headache d) Insomnia e) Neutropenia

Pre-Assessment 3 EF is a 33-year-old cisgender MSM, PWID who is here for routine HIV PrEP 3-month follow-up What monitoring do you recommend today? a) HIV test b) Renal function c) LFTs d) CBCs e) STI testing f) HCV test

Pre-Assessment 4 Which of the following medications are currently indicated for HIV PrEP?

a) Tenofovir Disoproxil Fumarate/Emtricitabine b) Tenofovir Alafenamide/Emtricitabine c) Tenofovir Alafenamide/Bictegravir Rx d) Dolutegravir e) Cabotegravir Pre-Assessment 5 GH is a 38-year-old cisgender woman in a monogamous relationship with a cisgender man who has HIV. She has been taking Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC) for HIV PrEP for the past 6 months. She asks you how Tenofovir Alafenamide (TAF/FTC) compares to TDF/FTC. Which of the following is FALSE? a) TAF/FTC can be used in CrCl >30 ml/min b) TAF/FTC has fewer bone mineral density effects than TDF/FTC c) TAF/FTC is indicated for HIV PrEP in receptive vaginal sex d) TAF/FTC can cause increased weight gain and triglycerides . Human Immunodeficiency Virus (HIV) . Retrovirus that attacks the body’s immune system . Originates from a type of chimpanzee in Central Africa Background: . There is no cure for HIV, but it can be PREVENTED HIV Infection and/or managed with lifestyle practices and medication treatment . Untreated HIV can lead to acquired immunodeficiency syndrome (AIDS) . The only way to know if someone has HIV is to get tested

HIV Lifecycle https://www.merckmanuals.com/professional/inf ectious-diseases/human-immunodeficiency-virus- hiv/human-immunodeficiency-virus-hiv- infection#v1021390 1 2 3

Stage 1 Stage 2 Stage 3 • Acute infection • Chronic Infection • AIDS • ≥ 500 cells/mcL • 200 - 499 cells/mcL • < 200 cells/mcL

The Stages of HIV Infection Acute HIV Infection

. 2-4 weeks after infection . Flu-like symptoms . Very infectious . Viral load: High . > 100,000 copies/mL . CD4+ cell count: ≥ 500 cells/mcL

https://www.cdc.gov/hiv/basics/whatishiv.html Chronic HIV Infection

. Viral Load: Low . CD4+ cell count: 200 to 499 cells/mcL . Also known as: . Clinical Latency . Asymptomatic HIV . May last decade or longer . Still infectious https://www.cdc.gov/hiv/clinicians/index.html

Acquired Immunodeficiency Syndrome (AIDS)

. Viral Load: HIGH . CD4+ cell count: < 200 cells/mcL Or ≤ 14% . Immunocompromised and subject to opportunistic infections . AIDS-defining illnesses . W/out treatment, life expectancy is ≈ 3 years . Very infectious

https://www.womenshealth.gov/hiv-and-aids/hiv-and-aids-basics

HIV Testing: Timeline to Detection

https://www.hiv.uw.edu/go/screening-diagnosis/acute-recent-early-hiv/core-concept/all HIV Incidence in 2018 in the U.S.

~1.2 million people currently living with HIV In the United States Estimated 36,400 new HIV infections in 2018

https://www.hiv.gov/hiv-basics/overview/data-and-trends/statistics

http://dhss.alaska.gov/dph/Epi/hivstd/Documents/HIV%20Surveillance%20Report%20- %20Alaska,%201982-2019.pdf

Ending the HIV Epidemic Ending the HIV Epidemic: A Plan for America

https://www.hiv.gov/federal-response/ending-the-hiv-epidemic/overview “Of the estimated 1 million Americans at substantial risk for HIV and who could benefit from PrEP, fewer than 10 percent are actually using this medication. Increasing PrEP use among high-risk groups could prevent almost 50,000 HIV infections by 2020.”

https://www.hiv.gov/federal-response/ending-the-hiv-epidemic/overview

. Access to Care . Cost Barriers . Stigma to HIV PrEP .LGBTQ+ .PWID . Provider Knowledge/Comfort Prescribing PrEP

HIV PrEP: Pre-Exposure Prophylaxis FDA-Approved HIV PrEP Medications 1. Emtricitabine 200mg/Tenofovir Disoproxil Fumarate 300mg (TDF/FTC or Truvada) a. FDA Approved in 2012 for HIV PrEP for adults and adolescents >35kg b. iPrEx, ATN 082, IPERGAY, PROUD, Partners PrEP, TDF2, VOICE, Bangkok Tenofovir Study, etc. c. Indicated for MSM, heterosexually active men and women, PWID at high risk of acquiring HIV d. Dose: 1 tablet PO once daily

2. Emtricitabine 200mg/Tenofovir Alafenamide 25mg (TAF/FTC or Descovy) a. FDA Approved in 2019 for HIV PrEP b. Discover Trial; compared to TDF/FTC c. For MSM and transgender women at high risk of acquiring HIV; not approved for receptive vaginal sex d. Dose: 1 tablet PO once daily

 Mechanism of action: HIV Nucleoside/Nucleotide Reverse Transcriptase Inhibition

https://clinicalinfo.hiv.gov/en/drugs

PrEP Efficacy: >90% sexual transmission >70% PWID Indications for HIV PrEP . Sex partner of HIV+ person not known to be virally suppressed for > 6 months . Condomless sex or inconsistent condom use with partner of unknown status known to be at substantial risk of HIV . Bacterial STI in the past 6 months . Multiple sex partners . History of nPEP (non-occupational Post-exposure Prophylaxis) use . Transactional sex or commercial sex work . PWID (People who inject drugs) and sharing needles or works https://www.cdc.gov/hiv/pdf/risk/prep-cdc-hiv-prep-provider-supplement-2017.pdf https://www.cdc.gov/hiv/pdf/risk/prep-cdc-hiv-prep-provider-supplement-2017.pdf . HIV Positive . Refer for HIV treatment start . Possible HIV exposure within 72 hours Contraindications . Offer nPEP x 28 days, repeat HIV testing, consider nPEP to PrEP for HIV PrEP transition . Creatinine clearance (CrCl) < 60ml/min (for TDF/FTC) . Creatinine clearance (CrCl) < 30ml/min (for TAF/FTC) . **Using Cockcroft-Gault formula Precautions for HIV PrEP . Hepatitis B infection: Hep B can flare if PrEP is discontinued . Tenofovir and FTC are active against Hep B . Check HBsAG and HBVsAb prior to initiation . Offer Hepatitis B vaccination, if non-immune . Potential drug resistance if PrEP is used in undiagnosed HIV infection . Renal monitoring more frequently if suspect kidney disease (diabetes) . Caution with medications that may reduce renal function . Bone Mineral Density: consider avoiding TDF in osteoporosis, adolescence . Pregnancy/Breastfeeding: not contraindicated; is off-label; discuss risks/benefits . HIV PrEP does not protect against other STIs; continue to use condoms

PrEP PEP or nPEP Common Pitfalls . PrEP is NOT a complete HIV regimen . Most recommended HIV regimens consist of a complete 3-drug regimen, such as an NRTI backbone (2 NRTIs) plus an INSTI . PrEP should NOT be used for nPEP (non-occupational Post-Exposure Prophylaxis) . nPEP should consist of a complete 3-drug regimen x 28 days, usually: . TDF/FTC plus raltegravir (BID) or TDF/FTC plus dolutegravir . nPEP should be started ASAP, within 72 hours of potential exposure to HIV . Continue to offer sexual risk reduction, harm-reduction counseling

HIV PrEP Monitoring Recommendations

.Baseline . HIV test negative within past week (ideally antigen/antibody test) . Renal function . Hepatitis B status . HCV test . STI testing, including syphilis . Pregnancy test .Every 3 months . HIV Test . STI testing (all sites of potential exposure: pharyngeal, rectal, urine NAAT) . Pregnancy test .Every 6 months . Renal function (more frequently if risk factors) .Annually: Reassess need for continued PrEP Side Effect Monitoring

TDF/FTC (TRUVADA) TAF/FTC (DESCOVY)

. Nausea . Nausea . Flatulence/Abdominal Pain . Diarrhea . Headache . Headache . Rash . Fatigue

. Decreased Bone Mineral Density . Increased triglycerides . Weight Loss HIV PrEP Prescribing . Provide no more than 90 days of medication per prescription . This helps ensure that patient adheres to appropriate follow-up every 90 days HIV Risk Reduction Efficacy as a Function of Adherence 100% 90% 80% 96% 99% 70% 60% 76% 50% 40% 30% 20% / 10% 0% Adherence 2 doses/week 4 doses/week 7 doses/week

The Importance of Adherence to PrEP: STRAND Trial (TDF dosing in MSM) Time To Achieve Protection . 7 days in rectal tissue . 20 days in cervicovaginal tissue . 20 days in blood

. Time for protective effect to wane: . 7-10 days after stopping . If patient wishes to restart after stopping PrEP >7 days, recheck HIV test prior to restart FYI: Off-Label “On-Demand PrEP” AKA “Intermittent Dosing” AKA “2-1-1” for MSM

IPERGAY (INTERVENTION PRÉVENTIVE DE L’EXPOSITION AUX RISQUES AVEC ET POUR LES GAYS)

1) 2 tablets (TDF/FTC) between 2 and 24 hours before sex

2) 1 tablet 24 hours after the first dose

3) 1 tablet 48 hours after the first dose

4) Continuing daily pills if sexual activity continues, until 48 hours after the last sex. Compare and Contrast PrEP Options

TDF/FTC (TRUVADA) TAF/FTC (DESCOVY)

• Creatinine Clearance must be ≥60ml/min • Creatinine Clearance must be ≥30ml/min • Approved for receptive vaginal sex • NOT approved for receptive vaginal sex • Potential Renal and Bone Mineral Density • Favorable Renal and Bone Mineral Density Effects Effects, compared to TDF • Weight neutral • Mild Weight gain • Small LDL decrease • Small LDL increase • Generic Available 2020 • Brand Only

Patient Access to HIV PrEP . Manufacturer medication assistance programs . Ready, Set, PrEP . Launched by DHHS in Dec 2019 . PrEP provided at no cost for patients with no prescription drug coverage . https://www.getyourprep.com/ . Provider or clinic prescribing PrEP . https://locator.hiv.gov/

In the HIV PrEP Pipeline . Cabotegravir 600 mg IM long-acting injection once every 8 weeks (after 4-week interval between initial 2 doses) . IAS-USA recommends for cisgender men and transwomen who have sex with men . Cabotegravir superior to TDF/FTC . HPTN 083: cisgender men and transwomen who have sex with men . HPTN 084: cisgender women . Dapivirine - Vaginal Ring . Every 28 days . Currently in use in Africa https://www.nih.gov/news-events/news-releases/vaginal-ring-hiv- prevention-receives-positive-opinion-european-regulator Post-Assessment Post-Assessment 1 AB is a 51-year-old transgender woman interested in starting HIV PrEP. She has the following: a) Recent HIV negative test b) Inconsistent condom use with partners of unknown HIV status, including PWID c) Treated for syphilis 3 months ago d) Has Hepatitis B infection e) CrCl = 28 ml/min Question: What of the above are indications or contraindications to HIV PrEP?

Post-Assessment 1 AB is a 51-year-old transgender woman interested in starting HIV PrEP. She has the following: a) Recent HIV negative test

Indications b) Inconsistent condom use with partners of unknown HIV status, including PWID c) Treated for syphilis 3 months ago d) Has Hepatitis B infection Contraindication e) CrCl = 28 ml/min Question: What of the above are indications or contraindications to HIV PrEP?

Post-Assessment 2 CD is a 22-year-old cisgender MSM (man who has sex with men) who started HIV PrEP 2 weeks ago. He believes he is having side effects. Which of the following are commonly reported side effects to PrEP medication? a) Nausea b) Abdominal pain c) Headache d) Insomnia e) Neutropenia

Post-Assessment 3 EF is a 33-year-old cisgender MSM, PWID who is here for routine HIV PrEP 3-month follow-up What monitoring do you recommend today? a) HIV test b) Renal function c) LFTs d) CBCs e) STI testing f) HCV test

Post-Assessment 3 EF is a 33-year-old cisgender MSM, PWID who is here for routine HIV PrEP 3-month follow-up What monitoring do you recommend today? a) HIV test Consider testing more b) Renal function frequently than every 6 months if risk factors present c) LFTs d) CBCs e) STI testing f) HCV test IAS-USA recommends every 3-6 months for PWID

Post-Assessment 4 Which of the following medications are currently indicated for HIV PrEP?

a) Tenofovir Disoproxil Fumarate/Emtricitabine b) Tenofovir Alafenamide/Emtricitabine c) Tenofovir Alafenamide/Bictegravir Rx d) Dolutegravir e) Cabotegravir Post-Assessment 4 Which of the following medications are currently indicated for HIV PrEP?

a) Tenofovir Disoproxil Fumarate/Emtricitabine b) Tenofovir Alafenamide/Emtricitabine c) Tenofovir Alafenamide/Bictegravir Rx d) Dolutegravir e) Cabotegravir Awaiting approval Post-Assessment 5 GH is a 38-year-old cisgender woman in a monogamous relationship with a cisgender man who has HIV. She has been taking Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC) for HIV PrEP for the past 6 months. She asks you how Tenofovir Alafenamide (TAF/FTC) compares to TDF/FTC. Which of the following is FALSE? a) TAF/FTC can be used in CrCl >30 ml/min b) TAF/FTC has fewer bone mineral density effects than TDF/FTC c) TAF/FTC is indicated for HIV PrEP in receptive vaginal sex d) TAF/FTC can cause increased weight gain and triglycerides Post-Assessment 5 GH is a 38-year-old cisgender woman in a monogamous relationship with a cisgender man who has HIV. She has been taking Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC) for HIV PrEP for the past 6 months. She asks you how Tenofovir Alafenamide (TAF/FTC) compares to TDF/FTC. Which of the following is FALSE? a) TAF/FTC can be used in CrCl >30 ml/min b) TAF/FTC has fewer bone mineral density effects than TDF/FTC c) TAF/FTC is indicated for HIV PrEP in receptive vaginal sex FALSE d) TAF/FTC can cause increased weight gain and triglycerides PrEP Resources . National Clinicians Consultation Center PrEPline at 855-448-7737 or http://nccc.ucsf.edu/clinician-consultation/prep-pre-exposure-prophylaxis/ . National PrEP Clinician Locator (https://preplocator.org/) .AIDS Info (http://www.aidsinfo.nih.gov, http://www.aids.gov) .The National Network of STD/HIV Prevention Training Centers ( http://nnptc.org/) .The AIDS Education Training Centers National Resource Center (http://www.aids-ed.org) Questions? References

1. Centers for Disease Control and Prevention: US Public Health Service: Preexposure Prophylaxis for the Prevention of HIV Infection in the United States – 2017 Update: Clinical Practice Guideline. https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines- 2017.pdf. Published March 2018. 2. Centers for Disease Control and Prevention: US Public Health Service: Preexposure Prophylaxis for the Prevention of HIV Infection in the United States – 2017 Update: Clinical Providers’ Supplement. https://www.cdc.gov/hiv/pdf/risk/prep-cdc-hiv-prep-provider- supplement-2017.pdf. Published March 2018. 3. Saag MS, Gandhi RT, Hoy JF, et al. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults. 2020 Recommendations of the International Antiviral Society–USA Panel. JAMA. 2020;324(16):1651-1669 4. Vail RM, Medical Care Criteria Committee. PrEP to Prevent HIV and Promote Sexual Health. New York State Department of Health AIDS Institute. https://www.hivguidelines.org/prep-for-prevention/ 5. Owens DK, Davidson KW, Krist AH, et al. Preexposure Prophylaxis for the Prevention of HIV Infection. US Preventive Services Task Force Recommendation Statement JAMA. 2019;321(22):2203-2213. 6. Boyette M, Jones SA. State of Alaska Epidemiology Bulletin: HIV Update – Alaska, 2019. http://www.epi.alaska.gov/bulletins/docs/b2020_14.pdf 7. Centers for Disease Control and Prevention: US Public Health Service: HIV Basics. https://www.cdc.gov/hiv/basics/index.html. Accessed 11 Jan 2021. 8. Cachay, E, M.D, MAS. Merck Manual – Human Immunodeficiency Virus (HIV) Infection. https://www.merckmanuals.com/professional/infectious-diseases/human-immunodeficiency-virus-hiv/human-immunodeficiency-virus- hiv-infection#v1021378. Accessed 11 Jan 2021.