The iPrEx Results: Lifting Hopes, Raising Questions
Thanksgiving week was a truly auspicious time for results to be released from the first clinical trial evaluating the use of antiretroviral treatment to prevent HIV infection among gay men and transgenders. There was much to be thankful for: Data from the iPrEx study showed that taking once-daily tenofovir/emtricitabine (Truvada), as part of a comprehensive HIV prevention package, reduced new infections by about 44%.
Thirty years into an epidemic disproportionately affecting gay men and other men who have sex with men, there is finally a study showing the efficacy of an HIV prevention strategy tested specifically in that population. Moreover, iPrEx proved the concept of pre-exposure prophylaxis (PrEP) -- taking antiretroviral drugs before exposure to HIV -- as a way to avoid infection.
The iPrEx study involved nearly 2,500 healthy, "high risk" gay men, transgender women and other men who have sex with men, and took place in 11 sites in Peru, Ecuador, Brazil, South Africa, Thailand and the United States (San Francisco and Boston). Participants were randomly assigned to take either one tablet of Truvada (a combination of tenofovir and emtricitabine) or a placebo once a day. Both study groups also received comprehensive HIV prevention information and services, including condom counseling and screening and treatment of sexually transmitted infections. (See "Tenofovir/Emtricitabine PreP Shows Protective Effect," in this issue, for details on the study design and outcomes.)
The results of the iPrEx study not only demonstrated that PrEP was effective in reducing HIV infection, but that it also appeared to work best among participants who used the study drug consistently. Compared with the placebo group, 50% fewer HIV infections occurred among participants who reported taking Truvada half the time, and 73% fewer infections occurred among those who reported taking the study drug on 90% or more days.
Blood levels of Truvada were compared in 34 people who acquired HIV during the trial and 43 people who remained HIV negative. Among those taking Truvada, the drug was detected in less than 10% of people who became infected and about half of those who remained HIV negative. This suggests that drug level in the blood was a good predictor of protection from HIV infection. So, taking the pill consistently makes a real difference.
But it is important to note that only about half of the iPrEx participants actually took their pills daily as prescribed by study protocol. As has been true in other HIV prevention trials, adherence -- taking the study product as prescribed -- is a core issue in determining whether and how well something works. Many people have difficulty taking a pill once a day every day, so it will be important to see whether knowing the actual efficacy of the pill makes a difference in how diligent people are in taking it. (Participants in the iPrEx study did not know whether they were taking Truvada or the placebo.)
The iPrEx study also showed that PrEP with Truvada was generally safe and well tolerated. Researchers found no differences in serious side effects between the Truvada and placebo groups, and those side effects that did occur -- such as nausea and unintentional weight loss -- were infrequent and mild. This is similar to what has been found in previous PrEP safety studies and among HIV positive people taking Truvada as part of their treatment regimen.
One very important finding from the iPrEx study was that, overall, participants in both the Truvada and the placebo arms reduced their HIV-associated behavioral risk during the trial period by increasing their condom use and decreasing their number of sex partners. This finding speaks to the impact of the comprehensive HIV prevention counseling provided during the study. It also raises the question of how much of the reduction in HIV infections observed was actually a result of the study drug and how much may have been due to behavioral risk reduction.
The efficacy of PrEP, although partial (that is, not reducing risk of HIV infection by 100%), raises a host of scientific, clinical, programmatic and policy questions that are being pursued by U.S. and global researchers, advocates, policy makers and funders. On the research front, a number of PrEP studies are underway or planned that will assess the efficacy of PrEP administered in different ways and among different populations. Most immediately, an 18-month open-label study of Truvada PrEP, which will provide the drug to any HIV negative participants in the original iPrEx study who wish to join, will begin early next year and is expected to provide more information about safety, efficacy and pill-taking behavior among those who now know what they are taking and how it appears to work.
This article was provided by San Francisco AIDS Foundation. It is a part of the publication Bulletin of Experimental Treatments for AIDS. Visit San Francisco AIDS Foundation's Web site to find out more about their activities, publications and services.
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