Biomedical HIV Prevention Research

1. Biomedical HIV Prevention Research Where are we? And where do we go from here? Mitchell Warren Executive Director, AVAC National Press Foundation @ IAS/Cape Town 17 July 2009

2. Prior to exposure Point of transmission After infection • Education & Behavior change • Male and female condoms • Anti-retroviral therapy (mother-to-child) • Post-exposure prophylaxis (PEP) • Anti-retroviral therapy • Care • Education & Behavioral change • Male circumcision • Preventive Vaccines • Pre-exposure prophylaxis (PrEP) • HSV2 suppression • TherapeuticVaccines • Topical (vaginal and rectal) microbicides • Diaphragm, cervical barriers & new FCs HIV/AIDS Toolkit

3. An expanded alphabet soup of prevention: ABC (male & female), clean needles, male circumcision, VCT, behavioral & structural interventions Prevention & Testing Deliver today Develop for tomorrow Treatment Trials Towards universal access Vaginal and rectal microbicides, PrEP, vaccines, cervical barriers… A comprehensive, integrated & sustained response

7. What is PrEP? • Experimental HIV prevention strategy that would use antiretrovirals (ARVs) to protect HIV-negative people from HIV infection • In this strategy, people would take a single drug, or a combination of drugs, before exposure to HIV, with the hope that it would lower their risk of infection • Possibility of daily dosing and intermittent dosing being tested • PrEP is not yet proven to work

8. Why the interest in PrEP? • Data from numerous animal challenge models show protection from PrEP • ARVs for PMTCT provides proof of concept in humans • Success of Post-Exposure Prophylaxis (PEP) for needlestick exposure in observational data • PrEP builds on the concept that medications can be used by healthy people to prevent some infections • Malaria prophylaxis for travelers • Assumption that stopping HIV replication as soon as virus enters the body may prevent permanent infection

9. Ideal PrEP Product Criteria • Safety profile – use for years in healthy individuals • Ease of use – once daily, weekly, intermittent, missed dose • Good drug penetration – at the viral portals of entry (rectum and genital tract) • High effectiveness – in real world situations • High barrier for resistance – requirement for multiple mutations to cause virologic failure • Limited impact on therapy – low or no level of cross resistance) • Cost effective and accessible Derdelinckx et al PLosMedicine 2006

10. Current PrEP Products Being Studies • Current oral PrEP trials are testing tenofovir disoproxil fumarate (TDF) and a combination of TDF plus emtricitabine (FTC) • TDF is marketed under the name Viread, and TDF/FTC is marketed under the name Truvada, both made by Gilead Sciences, Inc. • Also current trials of tenofovir gel as a topical microbicide

11. Why TDF and TDF/FTC? • Limited side effects • Strong safety profile as therapy among HIV positive people • Relatively long duration of action in the body (product “half-life”) • Less likelihood of promoting drug resistance compared to other ARVs

12. Current PrEP Studies • Seven current studies of daily oral PrEP; small intermittent study to start in July 2009 • Almost 20,000 participants currently or soon to be enrolled • Designed to produce results in diverse populations, representing multiple routes of transmission: • Men and women in high prevalence locations • Sero-discordant heterosexual couples • Injection drug users • Gay men &other men who have sex with men (MSM)

16. 2008 Investments in PrEP R&D From Adapting to Realities: Trends in HIV Prevention Research Funding, 2000 to 2008, HIV Vaccines and Microbicides Resource Tracking Working Group, July 2008

17. What questions will remain after the current trials? • Additional populations not in current trials, e.g. adolescents and pregnant women • Intermittent dosing schedules • Other possible drugs for PrEP • Potential resistance if infection does occur while on PrEP

19. Current (and Future) PrEP Challenges • Is it safe to give ARV drugs to uninfected people? • Will those who get infected while taking PrEP have HIV that is resistant to the PrEP antiretrovirals? Will this affect subsequent care and choice of ARV treatment? • Will people adhere to daily PrEP for long periods? • Is intermittent PrEP more acceptable, and is it safe and effective? • How often to do HIV testing on people on PrEP? • Is there behavioral disinhibition/risk compensation? • Is this an affordable and practical HIV prevention strategy for scale-up?

20. What Is Needed Now? • Ensure the current clinical trials have the best chance of producing decisive results. • Identify and invest in additional research. • Plan now for optimal use of PrEP. • Prepare for global procurement and delivery of PrEP. • Provide adequate financing.

21. For More PrEP Information from AVAC • Adapting to Realities: Trends in HIV Prevention Research Funding, 2000 to 2008, HIV Vaccines and Microbicides Resource Tracking Working Group (AVAC, AMD, IAVI, UNAIDS) – coming Monday, 20 July 2009 • www.prepwatch.org • The PrEP Implementation Puzzle: Many missing piecesfrom AVAC Report 2009: Piecing Together the HIV Prevention Puzzle • Anticipating the Results of PrEP Trials: A powerful new HIV prevention tool may be on the horizon. Are we prepared?, 2008 • Will a pill a day prevent HIV? Anticipating the results of the tenofovir PrEP trials, 2005 • PrEP Factsheet, 2009

22. About AVAC • Founded in 1995, AVAC is an international, non-profit organization that uses education, policy analysis, advocacy and community mobilization to accelerate the ethical development and eventual global delivery of AIDS vaccines and other new HIV prevention options as part of a comprehensive response to the pandemic. • We accept no government or pharmaceutical funding. • www.avac.org