The Body Covers: The XVI International AIDS Conference
Tenofovir for HIV Prevention: Early Results From PrEP Study Promising, but Inconclusive
August 17, 2006
While antiretrovirals have been increasingly used for post-exposure prophylaxis in recent years, data on the safety and efficacy of pre-exposure prophylaxis (PrEP) has been eagerly awaited, as researchers and advocates alike try to gauge its potential power as an HIV prevention tool. PrEP is the use of oral antiretrovirals by HIV-uninfected individuals prior to any potential exposure to HIV.
The antiretroviral that has received the most attention for its potential as a PrEP drug is tenofovir (TDF, Viread). At the XVI International AIDS Conference, the first early results were presented from a double-blind, placebo-controlled, international study of tenofovir as PrEP in women.1 (Actually, the results were reported by mainstream media well before the late-breaker presentation on Aug. 17, 2006. The reality is somewhat less glowingly positive than those media reports indicated.)
The study enrolled 936 HIV-uninfected, at-risk women in Cameroon, Ghana and Nigeria; data from 731 of those patients were presented at this conference. Approximately half of the women were randomized to receive 300 mg tenofovir daily, with the other half receiving a placebo. The planned follow-up period was one year. In Nigeria, however, substandard laboratory monitoring resulted in the cancellation of that country's PrEP trial, effectively invalidating any analysis of laboratory abnormalities from that site.
All of the women enrolled in the trial underwent a comprehensive informed consent process and rigorous education for risk reduction, including information on condom use, at monthly visits.
The results found a 65% decrease in HIV seroconversion in women who received tenofovir (0.86% per 100 person-years) compared with women who received placebo (2.48% per 100 person-years), although the difference did not reach statistical significance. The overall number of seroconversions was relatively low in both groups: two of the 363 patients in the tenofovir arm seroconverted versus six of the 368 patients in the placebo arm. There were low rates of potential study-related adverse events, with no difference between arms and no cases of renal dysfunction.
The study also found that, while there was an increase in the number of sex acts in the last seven days of the study, there was a decrease in the number of new partners and a very impressive increase in reported condom use during the last reported sexual encounter by all study participants -- from 52% reporting condom use to 94%. The highly effective prevention education that was given to study participants in both arms of the study may have resulted in lower rates of seroconversion than had been anticipated (two in the tenofovir arm and six in the placebo arm), decreasing the ability of the study to detect a significant difference in risk of HIV infection.
These data serve as the first glimpse of the potential efficacy of PrEP as a component of prevention efforts. The findings are of considerable interest to those searching for a female-controlled prevention method that could potentially be employed while other prevention tools, including microbicides, continue to be developed.
However, it was also emphasized that more studies are required to prove the efficacy of tenofovir as PrEP for preventing sexual and injection-related HIV transmission, and to further examine the potential for longer-term toxicity, not to mention the emergence of antiretroviral resistance among those who seroconvert despite receiving PrEP.
The significant difficulties encountered during the creation and execution of this study also highlighted the ongoing challenges of conducting PrEP studies. These challenges include:
Finally, it is critical to remember that even if PrEP is proven to be effective and safe over the long term, like all prevention methods, it must still be embedded in a comprehensive HIV prevention program that includes education and assistance in developing risk-reduction behaviors among HIV-uninfected individuals.
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