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

HIV/AIDS Toolkit
Prior to exposure
Education & Behavior change Male circumcision Preventive Vaccines Pre-exposure prophylaxis (PrEP) HSV2 suppression Diaphragm, cervical barriers & new FCs

Point of transmission
Male and female condoms Anti-retroviral therapy (motherto-child) Post-exposure prophylaxis (PEP) Topical (vaginal and rectal) microbicides

After infection
Anti-retroviral therapy Care Education & Behavioral change Therapeutic Vaccines

A comprehensive, integrated & sustained response
An expanded alphabet soup of prevention: ABC (male & female), clean needles, male circumcision, VCT, behavioral & structural interventions

Deliver today

Prevention & Testing Treatment Trials

Develop for tomorrow

Towards universal access

Vaginal and rectal microbicides, PrEP, vaccines, cervical barriers

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

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

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

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

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 ³half-life´)  Less likelihood of promoting drug resistance compared to other ARVs

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)

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

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

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?

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.

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  The PrEP Implementation Puzzle: Many missing pieces from 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

About AVAC 

Founded in 1995, AVAC is an international, nonprofit 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.

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