A highly anticipated trial to determine whether AIDS drugs taken by mouth can ward off HIV infection in women has been stopped early, a setback that surprised researchers after a string of successes in preventing transmission of the disease.
Researchers said Monday they had called off the trial among high-risk women in Africa because they wouldn’t be able to determine whether use of antiretroviral medication produced any benefit. The study tested whether taking the medication once a day could prevent uninfected women from contracting the AIDS virus, estimated to infect more than 2.5 million people each year.
Several researchers lamented the result as “disappointing” and surprising. The same prevention method was proved successful just 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.
Researchers speculated that participants in the most recent trial might not have adhered to the regimen as closely as the participants in the other trials. Physiological differences between men and women might also account for the differences between this trial and the one among gay and bisexual men.
But 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: in the tissues of the vagina.
In another surprise finding, women in the study taking the antiretroviral medication were more likely to get pregnant than women taking a placebo. This was true despite the fact that 96% of women in the study were on oral or injectable contraceptives when the study began.
There is no known interaction between the antiretroviral drugs and hormone contraceptives, said researchers. They said they would analyze their data to try to tease out if there might be such an interaction.
The randomized, placebo-controlled trial, called FEM-PrEP, was carried out among 1,951 women in South Africa, Kenya, and Tanzania by FHI, a non-profit health and development organization, with about $23 million in funding from the United States Agency for International Development and about $3 million from the Bill and Melinda Gates Foundation.
Approximately half the women were given Truvada, a pill that combines two antiretroviral medications, tenofovir and emtricitabine; the other half were given a placebo. Fifty-six infections occurred overall, with half among women taking a placebo and half among women taking the active drug.
Truvada is marketed world-wide by Gilead Sciences Inc., based in Foster City, Calif. In a statement Monday, the company said, “While this development is a disappointing one, Gilead believes that antiretroviral therapies remain a promising potential HIV prevention strategy.”
Clinical trials are typically reviewed at regularly scheduled intervals by an independent committee. Such a committee decided that, statistically, the FEM-PrEP trial could not answer the fundamental question of whether Truvada reduces the risk of HIV infection. So the committee recommended closing the trial. Two other studies in Africa are continuing that could resolve the issue of whether AIDS drugs taken orally can prevent HIV infection in women.
Last year, a study of Truvada among gay and bisexual men showed it reduced the chance of infection by about 44%. There is research, as yet unpublished, showing that the concentration of tenofovir, when taken orally, is higher in rectal tissue than in vaginal tissue, said Timothy Mastro, an FHI vice president who spoke on behalf of the study. If so, the men might have had more of the drug than the women at the site where they were exposed to the virus.
Last year, another trial in South Africa showed that women could be protected against HIV by applying to their vaginas before and after sex a gel containing tenofovir, one of the two medications in the pill taken by the women in the latest study.
However, research presented earlier this year at the Conference on Retroviruses and Opportunistic Infections showed tenofovir concentrations in vaginal tissue were about 100 times higher when the drug was applied in the gel form compared with when it was taken orally.
One question researchers raised is whether women in the study took the pill faithfully. Dr. Mastro said his team would address this question by examining whether stored blood samples contain the medication.[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article’s content, whether in support or in opposition.]