A major clinical trial attempting to show that daily use of the anti-HIV drug Truvada could prevent new HIV infections in heterosexual women was halted prematurely Monday when preliminary results indicated that the study "will be highly unlikely to be able to demonstrate the effectiveness of Truvada in preventing HIV infection in the study population, even if it continued to its originally planned conclusion," according to a statement released by Family Health International, which is overseeing the trial. The "surprising and disappointing" results came only six months after the release of data showing that the drug could reduce the infection rate by at least 44% in gay men, and by as much as 70% in those who used it consistently. That finding was hailed as a major breakthrough in AIDS prevention and researchers speculated that similar results would be obtained in ongoing studies in other population groups. But it was not to be.
In a "Dear Colleague" letter sent to physicians Monday by HIV experts at the Centers for Disease Control and Prevention, the experts cautioned women against using the drug for prevention. Some women have been using the drug off-label for that purpose, despite the lack of evidence of its efficacy.
Truvada, manufactured by Gilead Sciences Inc. of Foster City, Calif., is a combination of two drugs, tenofovir and emtricitabine. It is generally well tolerated and is already taken by an estimated 1.5 million people around the world for treatment of HIV infections. It is taken orally only once daily, which is thought to help ensure compliance with drug regimens.
The trial, called FEM-PrEP, was planned to enroll 3,000 HIV-negative women in Kenya, Tanzania and South Africa and continue through the end of 2012. As of April 18, 1,951 women had been enrolled, half of them receiving the drug daily and the other half receiving a placebo. A preliminary analysis of results by the data monitoring committee showed that 56 new HIV infections had been observed, half in the drug group and half in the placebo group. "At this time, it cannot be determined whether or not Truvada works to prevent infection in women," the Family Health International statement said, but it is clear that this study could not answer the question.
Researchers are at a loss to explain the results. Possibilities include: low adherence to the drug regimen; a true lack of effect of the drug in women, as opposed to the effect in gay men; or some other as-yet-unknown reason.
All of the women in the study were using contraception. The overall pregnancy rate was 9%, with the greatest incidence of pregnancies in the group of women taking oral contraceptives and receiving Truvada. That, some experts said, suggests that the lack of effectiveness of the drug may be due to lack of adherence, although it is possible that there is some previously unobserved interaction between the AIDS drug and contraceptives.
Side effects in the drug group were similar to those observed among people taking Truvada for HIV treatment, and included diarrhea, nausea, fatigue, headache, dizziness and rash.
The study was sponsored by the Bill & Melinda Gates Foundation and the U.S. Agency for International Development.