Results likely due to very low levels of product use with young, single women least likely to use strategies
Three antiretroviral-based strategies intended to prevent HIV infection among women did not prove effective in a major clinical trial in Africa. For reasons that are unclear, a majority of study participants-particularly young, single women-were unable to use their assigned approaches daily as directed, according to findings presented today by one of the study's co-leaders at the Conference on Retroviruses and Opportunistic Infections (CROI) in Atlanta.
The Vaginal and Oral Interventions to Control the Epidemic (VOICE) study, or MTN 003, was designed to evaluate the safety and efficacy of three HIV prevention strategies compared to placebo. Specifically, the trial tested an investigational vaginal gel containing the antiretroviral drug tenofovir, a pill form of tenofovir (brand name Viread), and a pill containing a combination of tenofovir and emtricitabine (brand name Truvada). The study was sponsored and largely funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
In the trial, the three strategies were tested among 5,029 sexually active women 18 to 45 years of age at 15 sites in South Africa, Uganda and Zimbabwe. Nearly half of the study participants were under the age of 25, and most were unmarried (79 percent). Participants in each of the three groups were counseled to use their assigned pill or gel once daily and received free condoms, ongoing counseling on how to reduce their HIV risk, and testing and treatment for sexually transmitted infections. Prior to enrollment, all potential study participants engaged in an oral and written consent process explaining the details of the study.
Study results presented today indicate that most VOICE participants did not adhere to the daily use schedule. Moreover, single women 25 years of age and younger were the least likely to use the investigational products and the most likely to become infected with HIV. The rate of new HIV infections among these young women was nearly 10 percent at some of the study sites in South Africa, reflecting a very high incidence of HIV infection among young women in these communities.
"We do not know why many participants in the VOICE study did not adhere to daily use of these HIV prevention strategies," said NIAID Director Anthony S. Fauci, M.D. "We must continue to conduct research to find additional HIV prevention tools that women will find acceptable and use consistently to protect themselves against infection."
In other HIV prevention studies involving different study populations, including men and women, both oral Truvada and oral tenofovir have demonstrated an ability to reduce the risk of HIV infection when used consistently. However, the VOICE study results are consistent with another clinical trial known as the FEM-PrEP study, which tested daily use of oral Truvada among a similar population of women. Like the VOICE study, researchers found that the majority of FEM-PrEP participants did not follow the daily regimen.
The VOICE study, which launched in 2009, was led by co-investigators Zvavahera Mike Chirenje, M.D., of the University of Zimbabwe in Harare, and Jeanne Marrazzo, M.D., M.P.H., from the University of Washington, Seattle. In fall 2011, oral tenofovir and tenofovir vaginal gel were dropped from the VOICE trial after separate routine reviews of the study data by an independent data and safety monitoring board determined that while each product was safe, neither was effective in preventing HIV compared with placebo. Researchers continued to evaluate oral Truvada until the study's scheduled conclusion in August 2012. Results presented today at the CROI meeting by Dr. Marazzo provided an analysis for each of the study's three product arms.
Of the 5,029 women who enrolled in the VOICE study, 312 became infected with HIV for an overall 5.7 percent rate of new HIV infections- reflecting a very high overall rate of infection among women in these areas. Twenty-two women were found to be HIV-infected at time of enrollment; therefore, the study's primary analysis was based on 5,007 participants.