Top 10 HIV/AIDS-Related Clinical Developments of 2011
December 1, 2011
In the iPrEx trial, published last year, we learned that among highly promiscuous men who have sex with men (MSM), daily oral Truvada (tenofovir/FTC) reduced their risk of acquisition of HIV by 44 percent -- a modest effect, but encouraging to many who look to ART as a chemical condom for those not interested in the latex kind.2 However, before we all cheer the advent of yet another little blue pill to make sex better, it would be nice to see if it also works in women, who often also have sex with men.
The FEM-PrEP study, designed to do just that, enrolled 1,951 women who were at high risk of acquiring HIV and who lived in Kenya, Tanzania or South Africa.3 All were randomized to daily oral Truvada or placebo. In April, a DSMB committee advised the investigators to close the study, as there was little chance that the trial would be able to demonstrate an effect of the intervention on transmission. Details regarding the outcomes are not fully available, but we do know that enrollment was hampered by a high rate (~20 percent) of HIV among women being screened for the study. The rate of new HIV infections among trial participants was 5 percent per year and, among the 56 new HIV infections that occurred, an equal number were in those participants assigned to Truvada as those assigned to a placebo.
On the heels of this announcement came a similar release from the VOICE (Vaginal and Oral Interventions to Control the Epidemic) study.3 This is a placebo-controlled study comparing daily use of oral Truvada versus oral Viread (tenofovir) alone versus a Viread-based vaginal gel in preventing male-to-female HIV transmission in South Africa, Uganda and Zimbabwe. In September, an independent monitoring determined that the oral Viread arm would be highly unlikely to be distinguishable from placebo and should be stopped. The other study arms continued until November when the safety board then determined that the Viread gel arm should also be stopped for reasons of futility. This leaves the Truvada arm, which will be observed.
The Bottom Line
We do not know for certain how well oral Truvada works as pre-exposure prophylaxis (PrEP) for women. Many suspect that poor adherence explains the lack of efficacy of Truvada in FEM-PrEP, and perhaps the Viread gel in VOICE. In the Partners PrEP trial, a different study that enrolled over 4,700 HIV-discordant heterosexual couples, oral daily Truvada provided a 73-percent-reduced risk of transmission (62 percent for women and 83 percent for men) compared to placebo and adherence was reportedly over 95 percent.4 Similarly, the TDF2 study, conducted in Botswana, found a 63-percent reduction in HIV acquisition among 1,219 men and women randomized to oral Truvada versus placebo.5 Again, in this study, adherence was measured to be high at about 84 percent. The study was not powered to detect differences in efficacy by gender. As far as the efficacy of the Viread gel, the CAPRISA study conducted in South Africa showed decent efficacy that, not surprisingly, was dependent on adherence.
While adherence may explain differences in study results, it may also provide a view of what the real-world experience will be when HIV-uninfected persons use ART to prevent their own infection. Unless interventions that blow away those being used to support ART adherence among HIV-positive patients can be developed, PrEP may turn out to be effective, but difficult to translate into practice.
There may also be biological explanations for gender differences in the efficacy of oral PrEP. Vaginas and anuses are just plain different and the ways in which drugs reach and remain active in the tissues of these orifices are not the same.
So for now, we are left with study results that are mixed when it comes to women and PrEP. Additional research will provide more data points. We will certainly learn more about the tissue activity of antiretrovirals in women and, further down the line, there will also be data looking at other agents, such as Selzentry (maraviroc, Celsentri), as PrEP in both men and women, as well as ART gels at different time schedules. Until then, we wait.
This article was provided by TheBody.
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