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 Point of transmission After infection

• Education & • Male and female • Anti-retroviral

Behavior change condoms therapy

• Male circumcision • Anti-retroviral • Care

therapy (mother-
• Preventive to-child) • Education &
Vaccines Behavioral
• Post-exposure change
• Pre-exposure prophylaxis (PEP)
• Therapeutic
prophylaxis
(PrEP) Vaccines
• Topical (vaginal and
rectal) microbicides
• HSV2 suppression
• Diaphragm, cervical
barriers & new FCs
A comprehensive, integrated & sustained response

An expanded alphabet soup of prevention:

ABC (male & female), clean needles, male circumcision, VCT,
behavioral & structural interventions

Prevention
Deliver & Testing Develop
today for tomorrow
Treatment Trials
Vaginal and
Towards universal access
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 “half-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
 www.prepwatch.org
 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, 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