Booty Butter Nectar of the Gods National Gay Men’s Health Summit October 2005, Salt Lake City

Why gay men need rectal microbicides and what we are doing about it. Presented by: Jim Pickett, Director of Public Policy AIDS Foundation of Chicago Why do gay men need rectal microbicides? Sexually, gay men are…

l Articulate l Creative l Loving l Adventurous l Fabulous l Fun l Playful l Uninhibited l Experimental l Literate l Versatile l Responsible We’re also risk takers… as human beings tend to be. Over 24 years into the HIV/AIDS epidemic l Fear/crisis fatigue. l Condom fatigue. l Navel to knee syndrome. l Different frames. l Complacency. l Sex ed, and the lack of. l HAART/optimism. l Desire for “raw”, “bareback”, i.e. natural sex. Prevention hasn’t effectively addressed…

l Intimacy. l Our relationships. l Value of fluid exchange. l Sero-sorting, nuanced sexual communications, e.g. “strategic positioning” l Risk equations. l Substance ab/use( “tina”, Viagra, alcohol). l Internet. l Depression. Mental health issues. l Partner violence. l Childhood sexual abuse. HIV/AIDS…the reality is:

l 4.2 - 5.8 million new HIV infections/year worldwide. l 2.5 - 3.5 million deaths/year worldwide. l Approx. 40,000 – 60,000 new infections in the U.S./year. l 2% HIV incidence among North American gay men/year. African American gay men especially impacted. HIV/AIDS… The reality is:

l Much of anal intercourse (AI) is unprotected. l In 2003, 35 - 48% of gay men reported having unprotected anal sex (research by Pamina Gorbach of UCLA). l AI is the primary mode of transmission for gay men. l The rectal mucosa is highly vulnerable. l Community surveys and STD rates (e.g. syphilis) in the West reveal the difficulty in maintaining high rates of condom use. Let’s not forget about the ladies

l U.S. hetero women 7x more AI than gay men. l Hello! l Approx. 1/4 have had AI. Condoms? l Women who have UAI 3-5x more likely than other women to become HIV+. l AI prevalence among heterosexual pop. underappreciated, represents significant risk for HIV transmission.

AI = anal Intercourse UAI = unprotected anal intercourse Gabriel Rotello LA Weekly – July 30, 2004

“We just kept wringing our hands and saying, ‘Why can’t we get everybody to use a condom all the time?’ You have to address the number of partners that people have. A 50 percent condom- use level is pretty good. If you can get 25 to 30 percent of the population to do something all the time, that’s considered really good. To get 100 percent is inconceivable, impossible, and it’s never happened.” Writer, activist. 1997 study – Sexual Ecology: AIDS and the Destiny of Gay Men "A strategy driven by fear of infection cannot succeed… long term success can only come through an approach based on values – the values of human rights and human dignity. Let us not forget that the Universal Declaration of Human Rights starts by placing dignity first." Irene Khan Secretary General Amnesty International Bangkok 2004 So what are the prevention options we have at our disposal?

Before we answer, let us reflect on the glorious marketplace that provides consumers with: l Reality television – 5,839 varietals l That we can now watch on our iPods l So many Blondes… burgers… l And make that a… Half-caf extra foam skim latte with Splenda, DOUBLE CUPPED. Are we satisfied with this? Donde esta el beef? Beyond the ABCs, beyond latex… The Rebel Gel , Super-improved Lube, Booty Butter, i.e. Microbicides

Something NEW for our prevention toolbox What are microbicides?

l They might take the form of lubricants, creams, gels, suppositories, douches, enemas… l Applied vaginally or rectally before sexual intercourse, offering protection from HIV and perhaps STD infections. How do/would microbicides work?

• Kill/inactivate/immobilize the virus. • Prohibit viral entry. • Inhibit viral replication. • Block infection by creating barrier between virus and cells. • Strengthen the body’s own natural defenses. • Ideally, a microbicide brought to market would combine these mechanisms for greater effectiveness Microbicide Clinical Trials October 2005 The Vaginal Pipeline

PHASE/TRIALS 1 ACIDFORM™/Amphora™ Carraguard® Cellulose acetate 1,2- benzenedicarboxylate (cellacefate/CAP) Cellulose sulfate/CS Lime juice TMC120 gel TMC120 vaginal ring UC-781 VivaGel/SPL7013™

© Alliance for Microbicide Development The Vaginal Pipeline cont…

1/2 Invisible Condom™

2 Praneem Polyherbal Protected Lactobacilli in combination with BZK Tenofovir/PMPA gel (1%) (HPTN 059) TMC120 gel

2/2B Tenofovir/PMPA gel (1%) and PRO 2000 (0.5%) BufferGel™ and PRO 2000 (0.5%) (HPTN 035)

3 Carraguard® Cellulose sulfate/CS PRO 2000 (0.5% and 2%) Savvy™(C31G) © Alliance for Microbicide Development Clinical Trial Sites

Antwerp, Belgium London, UK New York, USA Cincinnati, USA Washington, USA Providence, USA Philadelphia, USA Los Angeles, USA Baltimore, USA Houston, USA Norfolk, USA Ghana Birmingham, USA Côte d’Ivoire Miami, USA India Chiang Rai, Dominican Republic Nigeria Thailand Yaoundé, Cameroon Uganda Tanzania Malawi Zambia Zimbabwe Brazil Botswana South Africa

Alliance for Microbicide Development Four Primary Entities l The Population Council -- a not for profit group based in New York City l The HIV Prevention Trials Network -- a network of sites funded by the US National Institutes of Health l The MRC Research Collaborative --a network of sites funded by the UK government l The Global Microbicide Project -- a public sector research effort funded by the Bill & Melinda Gates Foundation Alliance for Microbicide Development www.microbicide.org Making the case l A microbicide that l Even a microbicide is only 60% that is 50% effective could effective and used prevent as many 30% of the time as 2.5 million could have a worldwide deaths substantial impact over three years, in a high risk even if only 20% of population, and people with access turn a source into used it 50% of the a sink (e.g. time they did not bathhouse.) use condoms. And how about that rectal pipeline?

Booty Butter next to the condoms and lube in aisle 12? Mind the gap l Vagina l Holey Trinity o Enclosed pouch o Anus-colon-rectum is one big open tube - 2 o Vagina is one tough ft up to spleen customer, the o The epithelium of epithelium is 40 cell rectum is very fragile, layers thick. 1 cell layer thick. o Different o Different environment, environment, ph, etc. ph, etc.

* Hormonal differences between M and F booty?

Rectal challenges - Biological l The rectum is very vascular, very lymphatic, and very vulnerable to infection. Any trauma (such as that caused by anal penetration) may facilitate HIV transmission. Rectal challenges - Biological

l HIV is present in the rectal mucosa of an HIV-positive person. l Cells in walls of rectum/colon designed to take up foreign particles and transport to immune cells for destruction. HIV takes advantage of this system. Rectal challenges - Biological l Fissures l Fistulas l Ulcerations l Hemorrhoids l HPV 50-70% gen pop l STDs l LGV - Lymphogranuloa Venereum Rectal challenges – Political, Cultural, Research, Funding

l Homophobia l Stigma around anal sex l Rectal research vulnerable l AHHHRRGHH! Don’t mention ANY orifice, let alone that! Non-biological Rectal Challenges, continued… l Politics, strategy – the need to be on the right radar and off the wrong radar l Vaginal competition l Insufficient funding l Pharma mostly not engaged l Small exceptions Tracking Funding for Microbicide Research and Development: Estimates of Annual Investments 2000 – 2005

“Over the last five years, funding for microbicide R&D from the public and philanthropic sectors has more than doubled, rising from US$ 65 mn in 2000 to US$ 142 mn in 2004 and, based on current commitments and disbursements for 2005, at least US$ 163 mn will be invested in 2005…”

(report released Aug 05) Tracking Funding for Microbicide Research and Development: Estimates of Annual Investments 2000 – 2005

“…In addition, in 2004 between US$ 3 mn and 6 mn was invested by the commercial sector. This total level of investment, however, falls far short of the US$ 280 mn per year that the International Partnership for Microbicides and the Alliance for Microbicide Development estimate will be required over the next five years to accelerate the search for a safe and effective microbicide.”

(report released Aug 05) Tracking Funding for Microbicide Research and Development: Estimates of Annual Investments 2000 – 2005

HIV Vaccines and Microbicides Resource Tracking Working Group

o AIDS Vaccine Advocacy Coalition (AVAC) www.avac.org o Alliance for Microbicide Development (AMD) www.microbicide.org o International AIDS Vaccine Initiative (IAVI) www.iavi.org o Joint United Nations Programme on HIV/AIDS (UNAIDS) www.unaids.org Funding Needs - IPM

l Research (as distinct from development) currently receives $65 million per year. l Estimated $130 million per year needed. l Next 5 years requires $280 million per year to accelerate search. l $130m research, $120m development, $20m site development, $10m advocacy l Where’s the rectal budget? Donde esta el beef?

IPM = International Partnership for Microbicides Rectal Research – A Summary l Dr. Ian McGowan, UCLA l Dr. Ken Mayer, Fenway l Dr. Alex Carballo- Dieguez, Columbia University l Dr. Craig Hendrix, Johns Hopkins University l Dr. John Hylton, Johns Hopkins University Rectal Research – A Summary l Product distribution studies l Rectal safety studies l RT inhibitor rectal microbicides l Formulation preference- Carballo-Dieguez, Mayer l Human acceptability studies l “Delivery of Microbicide to at Risk Intestinal l Volume escalation – Mucosa” – Hendrix Carballo-Dieguez, Mayer l “An Assessment of Sexual Practices Affecting the Feasibility of Microbicide Development” – Hylton Most of us use lubes. It may be assumed we’ll use microbicides. Current Research Program UCLA/McGowan l HPTN-056 Mucosal safety parameters l Microbicide Development Program (MDP) U19 l Aptamer Microbicide Development Program (AMDP) U01 l Ken Mayer Acceptability Studies

Slide courtesy of Dr. Ian McGowan Microbicide Development Program (MDP) U-19 Grant l Three projects l Preclinical evaluation of RT rectal microbicide candidates l Rectal health, behaviors, and product acceptability l Exploratory human trials of rectal microbicides l Three cores l Core A: Administration l Core B: Regulatory l Core C: Data management and biostatistics

Anton. 2004 Slide courtesy of Dr. Ian McGowan MDP-1 l Preclinical evaluation of RT rectal microbicide candidates l PMPA, UC-781, TMC-120 l In vitro cell lines l Ex vivo intestinal explant challenge studies l Macaque in vivo RT-SHIV challenge studies

Slide courtesy of Dr. Ian McGowan Say what?

l UC-781 – non-nucleoside reverse transcriptase inhibitor (Cellegy, formerly Biosyn). Investigational, not yet approved by the FDA for use outside clinical trials . l PMPA – Tenofovir/Viread (nucleotide analog from Gilead) l TMC-120 – experimental non-nucleoside reverse transcriptase inhibitor being developed by Tibotec, Belgian biotech company. TMC-120 development halted by Tibotec in 2003, decided to concentrate efforts on TMC-125, another NNRTI more easily absorbed in the body. In March 2004, Tibotec signed royalty-free agreement with International Partnership for Microbicides, to study TMC-120 as topical microbicide. MDP-2 l Rectal Health, Behaviors and Product Acceptability l Behavioral aspect of RAI in men and women l Anal symptomology & STIs in subjects practicing RAI l Acceptability of microbicide products

Slide courtesy of Dr. Ian McGowan MDP-3 l Exploratory Human trials of Rectal microbicides l Pre-clinical IND (Investigational New Drug) animal studies l Phase 1 safety study of UC-781 in HIV negative subjects l Phase 1 safety study of UC-781 in HIV seropositive subjects

http://mdp.ctrl.ucla.edu/

Slide courtesy of Dr. Ian McGowan What Do We Need to Do?

l Continue pipeline development l Establish safety parameters l Define regulatory environment l Increase funding ++ l Create Rectal Microbicide Trials Network l Accelerate timeframe for human Phase 1 studies l Advocate for rectal microbicide research

Slide courtesy of Dr. Ian McGowan Rectal Microbicide Symposium Cape Town April 23rd – 26th, 2006

http://www.microbicides2006.org/ Data break>>> Terrence Higgins Trust 2003 Gay Men’s Sex Survey

•>10,000 •Heard of •Would consider from web •PEP •21% •71% •Home HIV •22% •53% Test •Microbi- •23% •59% cides •Vaccine •66% •50%

PEP = post-exposure prophylaxis Advocacy – What’s happening? l Regional Working Groups - North America, Canada, England – Please join us! l www.LifeLube.org l Microbicide Development Act l Priorities and next steps www.LifeLube.org

l Focus on gay men l Sex Positive! l Acknowledgement of behavior, proposal of sexual harm reduction strategies, NO shrieking or clutching l Info clearinghouse l Engage opinion leaders, Gay Men’s Health movement, researchers, relationships l Microbicide advocacy in general, rectal in particular – Rectal Microbicide Working Group – JOIN US! l Media – cyber, bricks and mortar Microbicide Development Act of 2005 l What does the Act do? l Establishes a dedicated unit to microbicide research and development within the NIH’s National Institute of Allergy and Infectious Diseases -- thus creating a single line of administrative accountability and funding coordination. l Authorizes funding increases as needed at the CDC, NIH and USAID for the development of microbicidal products; and l Requires coordination between NIH and other Federal agencies supporting microbicide development, including the CDC and USAID. MDA status in the Senate

S.550 – introduced March 8, 2005 by Corzine, Snowe, Obama l Barbara Boxer [CA] l Dianne Feinstein [CA] l Christopher J. Dodd [CT] l Joseph Lieberman [CT] l Olympia Snowe [R-ME] l Richard J. Durbin [IL] l Jon Corzine [NJ] l Barack Obama [IL] l Frank R. Lautenberg [NJ] l Edward Kennedy [MA] l Jeff Bingaman [NM] l John F. Kerry [MA] l Hillary R. Clinton [NY] l Barbara A. Mikulski [MD] l Charles Schumer [NY] l Paul Sarbanes [MD] l Gordon Smith [R-OR] l Patrick J. Leahy [VT] l Maria Cantwell [WA] l Patty Murray [WA]

As of Sept 05 MDA status in the House H.R. 3854 introduced September 21, 2005 by Reps Shays, Schakowsky and Davis l Raul M. Grijalva [AZ-7] l James A. Leach [IA-2] l Fortney Pete Stark [CA-13] l Bobby L. Rush [IL-1] l Michael M Honda [CA-15] l Mark Steven Kirk [IL-10] l Howard L. Berman [CA-28] l Jesse L. Jr Jackson [IL-2] l Henry A. Waxman [CA-30] l Lane Evans [IL-17] l Juanita Millender-McDonald l Luis V. Gutierrez [IL-4] [CA-37] l Rahm Emanuel [IL-5] l George Miller [CA-7] l Danny K. Davis [IL-7] l Barbara Lee [CA-9] l Melissa L. Bean [IL-8] l John B. Larson [CT-1] l Janice D. Schakowsky [IL-9] l Christopher Shays [CT-4] l James P. McGovern [MA-3] l Robert Wexler [FL-19] As of Sept 05 House status cont.

l Chris Van Hollen [MD-8] Ø What can YOU do to help? l Donald M. Payne [NJ-10] Please contact your Legislators to urge them to l Major R. Owens [NY-11] support the new Microbicide l Michael R. McNulty [NY-21] Development Act by signing l Joseph Crowley [NY-7] on. Thank them for their l Sherrod Brown [OH-13] vision if they already have. l Allyson Y. Schwartz [PA-13] Visit http://www.global- campaign.org/get_involved.ht l Jim McDermott [WA-7] m to find the latest information and download a fact sheet.

As of Sept 05 Advocacy priorities and next steps l Prepare paper on activities, gaps & needs l Stimulate and advocate for research l Advocate for safety data on current vaginal products l Analyze current lubricant safety – Astroglide/DeLube – market share - advocacy l Build constituency l Resource development & awareness (MDA) l Networking,strategic alliances, relationships Campaign to End AIDS l“Ramp up HIV prevention at home and abroad, guided by science rather than ideology.” lwww.c2ea.org October 1, 2005 Michigan Ave, Chicago Words of Wisdom

l Summary of remarks made by Geeta Rao Gupta, International Center for Research on Women (DC),at Microbicides 2004: l We must manage expectations. l We must prepare for failure, and success. l We must work ahead of access timeline. Contact info:

l Jim Pickett [email protected] or 312-334-0920 l AIDS Foundation of Chicago www.aidschicago.org l LifeLube www.lifelube.org l Global Campaign for Microbicides www.global-campaign.org Thank you.