A three-country study has been halted after daily doses of the antiretroviral (ARV) Truvada, used as a pre-exposure prophylaxis (PrEP), failed to prevent HIV infection in the women participating.
Family Health International (FHI) will begin closing FEM-PrEP trial sites in Tanzania, Uganda and South Africa after early results showed no difference in the rate of HIV infection among women taking the ARV and those taking the placebo.
Pre-exposure prophylaxis would involve giving a daily dose of a single ARV drug to people who were HIV-negative but at high risk.
Results surprizing, disappointing
The results were both surprising and disappointing after several PrEP success stories, but researchers would start analysing the data and blood samples to pinpoint why the drug did not work, said Dr Timothy Mastro, FHI Vice President of Health and Development.
The results might be due to missed doses among patients, or an initial indication of Truvada's ineffectiveness as an HIV prevention strategy for women when taken orally.
Why study was unsuccessful
"There are a number of [reasons] for why the study may not have been successful. We used the same product as the iPrEX [Pre-Exposure Prophylaxis Initiative] study [a previous project] but ... in that study, the primary mode of HIV transmission was receptive anal intercourse," Mastro told IRIN/PlusNews.
The iPrEX study showed that a daily dose of Truvada reduced the risk of HIV infection among men who have sex with men (MSM), a high-risk group, by about 44%. Mastro said the United States Centres for Disease Control was drafting guidelines for the use of Truvada by MSM.
"Our study population [this time] was mainly at risk for HIV through vaginal intercourse, and there are substantial transmission dynamics. Drugs taken orally are distributed [in the body] in quite a different way than those taken topically," he said.
In July 2010, a study by the Centre for the AIDS Programme of Research in South Africa (CAPRISA) released the first positive results from a microbicide trial when it found that a vaginal gel containing the ARV, tenofovir, a component of Truvada, was 54% effective in preventing HIV infection in women who consistently applied it before sex.
"In the CAPRISA study the concentration of drugs in the rectal tissue is very different to that in vaginal tissues, so that could have been a factor [in the FEM-PrEP trial]," Mastro noted.
Although the FEM-PrEP study, in which 1,950 women took part, might not have shown positive results, Mastro said it could inform the work of researchers in similar ongoing trials, such as the VOICE microbicide study.
"It will be very important to fully analyse the data so we understand the findings and can compare our results with those from ongoing studies. In the scientific process we learn something from every step," he commented.
FHI researchers will be evaluating blood samples taken from the roughly 60 women who became HIV-positive during the study to check for the presence of drug-resistant HIV strains, some of which can develop when patients adhere poorly to an ARV drug regimen.
Scientists will also be seeking an answer as to why the women who took Truvada had a higher pregnancy rate than their peers on the placebo, despite reportedly taking birth control medication. Mastro said this might also be due to poor adherence to oral contraception, or Truvada might have interacted with the birth control drugs to weaken their contraceptive effects.
"The iPrEX study demonstrated the safety and efficacy of the use of Truvada [by MSM] for HIV prevention, and that remains valid," he told IRIN/PlusNews. "At this time, we simply don't know the safety or the efficacy for women." - (PlusNews, April 2011)
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