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IAS 2011: HIV PrEP Effective for Heterosexuals, Discordant Couples

Two studies find that pre-exposure prophylaxis (PrEP) with tenofovir or tenofovir/emtricitabine reduces the risk of HIV infection among heterosexuals and serodiscordant couples, researchers reported at IAS 2011.

Pre-exposure prophylaxis, or the use of antiretroviral drugs by HIV negative people to prevent infection, is an emerging biomedical approach to HIV prevention. Several studies have been presented at scientific conferences or reported in peer-reviewed journals, with somewhat differing results.

The iPrEx trial, a study of PrEP in men who have sex with men (MSM) and transgender women, found an overall 44% reduction in HIV infections for people taking tenofovir/emtricitabine (Truvada) compared to placebo. In people with detectable drug in their blood -- a strong indicator of adherence -- the efficacy was over 90%.

However, another study, called FEM-PrEP, found no prevention benefit for women using the same PrEP regimen. The results from FEM-PrEP were preliminary and more detailed analyses are planned, in particular to see if adherence had an effect on infection rates.

In an oral presentation at the 6th International IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011) last week in Rome, researchers presented data from 2 more PrEP studies, after initial results were announced the previous week. These studies, done in different populations than iPrEx, add to the evidence that PrEP is an effective tool for preventing HIV infection.

TDF2

The first study, called TDF2, was presented by Michael Thigpen of the U.S. Centers for Disease Control and Prevention (CDC). TDF2 was a double-blind placebo-controlled clinical trial measuring the efficacy of PrEP.

The study enrolled 1200 HIV negative people in Botswana, 45% of whom were women. Participants were randomly assigned to take either tenofovir/emtricitabine or placebo. Study medication or placebo were distributed monthly and participants were tested monthly for HIV infection. All participants were counseled about safer sex and drug adherence and provided with free condoms.

Results

• There were a total of 33 new HIV infections in the study: 9 in the PrEP arm and 24 in the placebo arm.
• This difference represented a 62.6% reduction in risk of infection.
• Looking only at people who were infected within 30 days of their last medication visit (while the drugs were still presumably active), there were 23 infections -- 4 in the PrEP arm and 19 in the placebo arm -- or a 77.9% reduction in risk.
• Overall, PrEP was only 49.4% effective in women; when looking at people infected within 30 days of their last medication visit, however, PrEP was 75.5% effective.
• 2 participants developed drug resistance during the study, 1 in each arm.
• 89.0% of people in the PrEP arm reported 1 or more adverse events compared to 85.6% in the placebo arm, a statistically significant difference.
• The rate of serious adverse events was less than 10.0% in both arms and did not differ between them.
• There were no significant differences in laboratory abnormalities, adherence, or frequency of sexual contact in the 2 arm.

Following up on these results, the CDC has expressed 3 immediate priorities: 1) conducting additional analyses, 2) open provision of Truvada for study participants for a year, 3) review and begin to work with partners to develop interim PrEP guidance for heterosexuals.

Partners PrEP

Jared Baeten from the University of Washington presented the second study, called Partners PrEP. This was a randomized, controlled 3-arm study comparing tenofovir (Viread) alone versus tenofovir/emtricitabine versus placebo for serodiscordant couples.

The study was conducted in Kenya and Uganda. A total of 4747 couples were enrolled, allocated equally to the 3 treatment groups. The average age of participants was 33 years. Couples had been together for 7 years on average and 98% were married; 38% of the HIV positive partners were women.

Results

• There were a total of 78 new infections: 18 in the tenofovir arm, 13 in the tenofovir/emtricitabine arm, and 47 in the placebo arm.
• Tenofovir was 62% effective in preventing HIV infection compared to placebo and tenofovir/emtricitabine was 73% effective.
• The difference between the 1-drug and 2-drug PrEP arms was not statistically significant.
• PrEP was equally effective for men and women.
• Overall rates of adverse events were low in the study, but diarrhea was more common in the PrEP arms.
• 27% of participants reported some unprotected sex and 33% reported sex outside of the relationship; there was no difference in reported sexual activity between the groups.

Thigpen said these results are "significant and welcome news for the populations hardest hit by epidemic." These 2 studies, taken together with the earlier results from iPrEx, suggest that PrEP could be an effective strategy for preventing HIV infection. Further analyses of the results from FEM-PrEP are being performed, which may help explain that study’s discordant results.

Commentary

There are many issues to work out around the implementation and use of PrEP. All of the PrEP studies fully analyzed to date have found significant differences in efficacy based on treatment adherence. As iPrEx principle investigator Robert Grant said during the conference, “We know PrEP works for people who are able to take it regularly.” Adherence education and support will be critical in any efforts to implement PrEP.

While the results of these studies have been uniformly welcomed, some policymakers and activists have expressed reservations. Who will use it? Who will pay for it? Will it get to the people who need it most? Can we afford to give antiretroviral drugs to HIV negative people when millions of HIV positive people worldwide do not have access to treatment? These are some of the important questions being asked about PrEP, and they will all need to be addressed. Resources dedicated to HIV prevention, treatment, and research are limited, and there is no agreement on the best way to allocate them.

We now know that condoms, clean needles, male circumcision, prophylaxis to prevent mother-to-child transmission, and treatment as prevention work. We also know that PrEP works for men who have sex with men and transgender women, and there is conflicting but generally positive evidence of its effectiveness for heterosexuals. Vaginal and anal microbicides are another promising approach currently being studied.

Having a diverse array of effective prevention options can go a long way to controlling and possibly halting the HIV/AIDS pandemic. While more research is needed to better understand the new approaches of PrEP and treatment as prevention, drug companies, policymakers, and communities affected by HIV must do even more work to meet the challenges presented by these welcome advances and to maximize their impact. As UNAIDS Executive Director Michel Sidibé said at the IAS meeting, “We have to remember that history will judge us not by our scientific breakthroughs, but how we apply them.”

7/26/11

References

MC Thigpen, PM Kebaabetswe, DK Smith, et al. Daily oral antiretroviral use for the prevention of HIV infection in heterosexually active young adults in Botswana: results from the TDF2 study. 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011). Rome, July 17-20, 2011. Abstract WELBC01.

J Baeten and C Celum. Antiretroviral pre-exposure prophylaxis for HIV-1 prevention among heterosexual African men and women: the Partners PrEP Study. 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011). Rome, July 17-20, 2011. Abstract MOAX0106.