Researchers to wind down HIV prevention trial in women after interim results find drug not offering protection from HIV

Researchers on Monday announced they were calling off a trial to test whether taking an oral HIV drug reduces the risk of HIV infection in women after interim analysis of the study showed women taking the medication were no less likely to become infected with HIV than those who were not taking the medicine, the Associated Press reports (4/18).

For the trial, researchers "tested women in Kenya, South Africa and Tanzania who were not already infected with HIV, the virus that causes AIDS," Reuters reports. Scientists believe that treating patients with low doses of HIV/AIDS medications, a concept known as "pre-exposure prophylaxis," or PrEP, can help to reduce a person's risk of becoming infected with HIV. For the FEM-PrEP trial, women took "Truvada, a drug made by Gilead that combines two antiretroviral drugs in a single pill," once a day. Previous studies have revealed the drug to be "safe and effective as a treatment for people who already have HIV," the news service adds (Clarke, 4/19).

"As of February 18, 2011, the study had screened 3,752 women and enrolled 1,951," according to a press release from Family Health International (FHI), the nonprofit group that was conducting the trial. "A total of 56 new HIV infections had occurred, with an equal number of infections in those participants assigned to Truvada and those assigned to a placebo pill," the release states (4/18).

"Several researchers lamented the result as 'disappointing' and surprising," the Wall Street Journal reports. "The same prevention method was proved successful last year in a multicountry trial among gay and bisexual men. Moreover, an AIDS drug applied to the vagina in a topical gel - rather than swallowed as a pill - demonstrated a protective effect last year among women," the newspaper writes (Schoofs, 4/19).

"These findings by no means suggest we should not do further PrEP trials in women," said Kevin Fenton, head of AIDS programs at the CDC, according to the Washington Post. "This really underscores the complexity of HIV prevention and the importance of doing multiple trials in different populations," he added.

Researchers Present Several Theories On Preliminary Results

The Washington Post summarizes several theories as to why the prevention method failed to work, including the possibility that adherence to the drug regimen was low (Brown, 4/18).

The Los Angeles Times' "Booster Shots" blog notes that all of the women in the study were taking contraceptives. However, "[t]he overall pregnancy rate was 9%, with the greatest incidence of pregnancies in the group of women taking oral contraceptives and receiving Truvada," compared with those taking a placebo, according to the blog. "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" (Maugh, 4/18).

According to the New York Times, "[m]ore women taking Truvada complained of unpleasant side effects, and therefore a greater number might have failed to adhere to the program." Each month, researchers asked the women enrolled in the trial how often they took the medications, and blood samples also were taken to confirm drug adherence. These data have yet to be analyzed, according to the newspaper (McNeil, 4/18).

"Aside from reporting issues, there could also be a biological explanation of why the protective effect found among gay men [taking Truvada] was not seen in women," TIME's "Healthland" blog writes. "There may be a physiological difference in how men and women acquire HIV, since different tissues are involved during sexual contact - vaginal mucosa for women, and rectal mucosa for men. HIV may preferentially infect one type of tissue over the other, or there could be other physiological reasons for the gender-based differences in infection rates," the blog adds (Park, 4/18).

In addition, a "particularly intriguing hypothesis, supported by other research, is that swallowing a pill might not lead to high enough drug concentrations at the site where HIV enters a woman," the Wall Street Journal continues (4/19).

"There are still too many unanswered questions for us to make any conclusions about the role of [using antiretroviral medications to prevent HIV] in women," Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said, according to TIME's "Healthland" blog. He emphasized that additional trials would be needed to determine whether oral PrEP offers women protection against HIV (4/18).

"While we are disappointed in the news from the FEM-PrEP study, funded by PEPFAR through USAID, other research on pre-exposure prophylaxis is underway," Ambassador Eric Goosby, U.S. global AIDS coordinator, and USAID Administrator Rajiv Shah said, according to a USAID press release (4/18). According to the AP, two other clinical trials testing PrEP "are under way in Africa, in heterosexual women and in couples where one has the virus and the other does not. Results are expected within two years" (4/18).

"We will continue to work with our colleagues in the scientific community to monitor the results of these and other research studies, in the hope that they will produce new tools for HIV/AIDS prevention," Goosby and Shah added, according to the release (4/18). The FEM-PrEP study, which cost $26 million, was supported by USAID and the Bill & Melinda Gates Foundation, according to the Washington Post (4/18).