Pre-exposure prophylaxis, or PrEP, is a strategy that involves use of antiretroviral medications (ARVs) to reduce the risk of HIV infection in HIV-negative people. PrEP is an HIV prevention strategy that doesn’t need to be used at the time of sex. This offers women and men an HIV risk-reduction option that can be used without negotiating with their partners.
In July 2012 daily TDF/FTC was approved by the US Food and Drug Administration for use as PrEP for HIV prevention in HIV-negative women and men. Daily TDF/FTC has been proven effective at reducing risk of HIV via sexual exposure in heterosexual men and women, gay men and other men who have sex with men, and transgender women. The TDF/FTC approval marked the first time a drug was approved for reducing HIV risk via sexual exposure.
Table of Contents
- VOICE Trial Results
- PrEP and Women in the US
- Guidance on PrEP Usage
- What PrEP Is—And What It Isn’t
- What We Know Now: Data to Date
- From Research to Rollout
- Challenges of Clinical Trial Design, Degree of Evidence and Recommendations in the Era of PrEP
VOICE Trial Results
Results from a large-scale HIV prevention trial among African women known as VOICE (Vaginal and Oral Interventions to Control the Epidemic) provide an urgent reminder that products must meet the needs of the people using them. While disappointing, the results lend new urgency and direction to the search for additional safe and effective HIV prevention options for women.
For the latest on the VOICE trial visit www.avac.org/voice.
PrEP and Women in the US
Working Group on US Women and PrEP:
The US Women and PrEP Working Group, a coalition of more than 50 women from leading AIDS and women’s health organizations, calls on US government agencies to coordinate a national agenda that will quickly and accurately answer questions about how the antiretroviral (ARV) drug Truvada can best be made available as an HIV prevention option for women at risk of HIV infection.
- Coalition of US Women’s Health and HIV Advocates Call for Accelerated US Government Plan for Demonstrating Feasibility of PrEP for Women
- Working Group on US Women and PrEP Statement
- US Women and PrEP Working Group Position Statement: Key points
To join the Working Group, or learn more, e-mail firstname.lastname@example.org.
- Will and should women in the US use PrEP? Findings from a focus group study of at-risk, HIV-negative women in Oakland, Memphis, San Diego and Washington, DC — Judith D. Auerbach, Alyx Banyan and Maura Riordan, July 2012
- Pre-exposure Prophylaxis for the Prevention of HIV Transmission to Women in the United States — Erika Aaron and Deborah Cohan, August 2012
- Comments to the FDA’s Antiviral Drugs Advisory Committee Meeting May — Erika Aaron, May 2012
Guidance on PrEP Usage
World Health Organization
- Guidance on oral PrEP for serodiscordant couples, men and transgender women who have sex with men at risk
US Centers for Disease Control
The British HIV Association/British Association for Sexual Health and HIV
Southern African HIV Clinicians Society Consensus Committee
What PrEP Is—And What It Isn’t
In the clinical trials, daily TDF/FTC helped prevent HIV among HIV-negative adults when used with condoms and other HIV prevention methods. The observed benefit was seen among participants who also received monthly HIV testing, counseling, condoms, treatment for sexually transmitted infections and other services.
TDF/FTC (marketed at Truvada) is the only drug FDA-approved for use as PrEP. This pill contains a combination of two drugs, TDF and FTC. There is positive data from one study of TDF alone, but it is has not been approved as PrEP by any regulatory agency. Other HIV drugs are being considered for oral PrEP, but there.
You can still get HIV when taking PrEP. Each of the large-scale trials of PrEP using daily TDF/FTC found that it is only partially effective. It should be used with safer sex practices and other HIV prevention methods.
PrEP is not a “vaccine” or a “morning-after” pill. The strategy as studied involves ongoing pill-taking. Daily TDF/FTC is only effective when taken consistently. In the trials, participants who reported taking the TDF/FTC pill consistently had the highest levels of protection.
What We Know Now: Data to Date
PrEP using a daily oral TDF/FTC tablet reduces risk of HIV in women and men.
Data from the iPrEx, Partners PrEP and TDF2 studies shows that daily oral TDF/FTC (marketed as Truvada) is safe and effective to reduce risk of infection in heterosexual men and women, gay men and other men who have sex with men, and transgender women.
Data from these studies formed the basis of Gilead’s application to the US Food and Drug Administration for approval of TDF/FTC as PrEP (Gilead is the manufacturer and patent holder for TDF/FTC). Trial data show that TDF/FTC reduces HIV risk in women and men who are able to take it correctly and consistently.
The estimates of effectiveness vary in each trial but across the studies adherence—or whether participants took the tablet daily as instructed—was predictive of protection. A trial of daily TDF/FTC in women, the FEM-PrEP trial, found no effect of daily oral TDF/FTC.
Further analysis of the FEM-PrEP data showed that the participants didn’t adhere well to the daily PrEP regimen. In fact, adherence was too low for the trial to ultimately determine whether the intervention provided any protection.
Bottom line: Daily TDF/FTC as PrEP works when taken correctly and consistently.
There is data on daily TDF from the Partners PrEP study, which showed that it worked to reduce risk in heterosexual men and women. Daily TDF was also tested in women in the VOICE trial, but it was not effective in women in that study. Data analysis is underway to better understand the result.
Daily TDF is also being tested for effectiveness in reducing risk of HIV via needle exposure. Results from a study in injecting drug users in Thailand are expected in early 2012.
From Research to Rollout
The first PrEP proof-of-concept data came from the iPrEx PrEP trial in November 2010, which showed that daily TDF/FTC can reduce HIV risk in MSM and transgender women—the following July data from Partners PrEP and TDF2 showed that the same regimen can reduce the risk of HIV in heterosexual men and women.
As promising as PrEP may be, significant questions remain unanswered, chief among them being whether the efficacy that was demonstrated within the confines of a clinical trial—where people were not certain whether they were taking drug or placebo, were told that the safety and efficacy of PrEP was unknown, and in which they received extensive monitoring and support—can be translated into effectiveness in practice.
Such clinical translation efforts are not unique to PrEP and can be expected with the introduction of any new biomedical advance for any disease. But, in particular, this translation effort is needed now in order to achieve the public health benefit for which PrEP is so promisingly suited—progress in reducing HIV infections.
A new option exists but who needs it, wants it and how can it be delivered for maximum impact? There are a number of different research initiatives ongoing to help answer these questions: open-label extension studies, demonstration projects and bridging studies.
Demonstration Projects and Implementation Pilots: TDF/FTC as PrEP has proven effective in the context of a controlled clinical trial environment—it’s not clear yet how it might work in the real world, without the intensive support and monitoring available in a clinical trial setting.
Demonstration project and implementation pilots are designed to better understand how to optimize PrEP programming in a real-world setting. These projects will focus on what PrEP implementation looks like when it is actually delivered in a clinic setting and will collect data.
Challenges of Clinical Trial Design, Degree of Evidence and Recommendations in the Era of PrEP
In January AVAC collaborated with the French AIDS funder and advocacy organization Sidaction to host a meeting in Paris on PrEP. Slides from the meeting are available below.
- Introduction— Dr. Constance Delaugerre, Hopital Saint-Louis & Sidaction, France
- Where are we now? A review of recent results, current and planned trials — Mr. Mitchell Warren, AVAC, USA
- Moving from Research to Implementation: What we still need to know — Dr. Kevin O’Reilly
- Evaluating interventions without placebo controls — Prof. Benoit Masse, University of Montreal, Canada
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