A study involving women at risk of HIV infection has discontinued a comparison of daily Viread (tenofovir) pre-exposure prophylaxis (PrEP) to placebo, in light of expert projections that the clinical trial will not be able to demonstrate effectiveness, according to a September 28 Microbicide Trials Network (MTN) announcement. The Vaginal and Oral Interventions to Control the Epidemic (VOICE) study will, however, continue evaluating the safety and efficacy of another oral tablet, Truvada (tenofovir plus emtricitabine), along with a vaginal microbicide containing tenofovir.
Though PrEP has been proven at least moderately effective in a large international study of men who have sex with men (MSM), its efficacy among women in studies has been checkered.
A study reported in April 2011, dubbed FEM-PrEP, yielded disappointing results. According to a planned interim check of the data, the study monitors found an equal number of new HIV infections among women using Truvada PrEP compared with those using placebo.
All eyes then fell on the African Partners PrEP and TDF2 studies to determine whether antiretrovirals (ARVs), used by women (and heterosexual men) at risk for HIV infection, could potentially serve as an effective prevention tool.
In Partners PrEP, Viread and Truvada reduced the risk of contracting HIV by 62 percent and 73 percent, respectively, among mixed-status heterosexual couples.
In TDF-2, which was primarily designed as a safety study, Truvada reduced new HIV infections by at least 63 percent among mostly single heterosexual men and women. However, some gender differences were noted by the researchers. Throughout the study, there were seven infection among women in the Truvada group and 14 infections among women in the placebo group, but this difference was not statistically significant, meaning it could have occurred by chance. Among men, with two and 10 infections respectively, the difference was statistically significant.
With the VOICE Data and Safety Monitoring Board (DSMB) recommendation to stop the Viread arm of the study, for the same reason cited during the review of the FEM-PrEP interim analysis, the potential utility of PrEP for women remains unclear.
VOICE involves 5,029 women at 15 trial sites in Uganda, South Africa and Zimbabwe. The trial is being conducted by the MTN, an HIV/AIDS clinical trials network funded by the National Institutes of Health.
The study was designed with five study groups: tenofovir gel, an inactive placebo gel, oral Viread, oral Truvada and an inactive placebo tablet, all taken once daily. VOICE is the only trial evaluating the daily use of PrEP and a vaginal microbicide in the same study.
On September 16, 2011, the National Institute of Allergy and Infectious Diseases (NIAID) Prevention Trials DSMB reviewed VOICE study data for the period between September 9, 2009, when the study began, and July 1, 2011. Based on this interim review, the DSMB determined that it was not possible to show whether oral Viread tablets were any better than a placebo for preventing HIV in the women assigned to that study group.
The DSMB recommended that the women randomized to the oral Viread group discontinue their use of the study medication. The MTN researchers did not cite any actual data—notably HIV infection rates among those taking Viread tablets compared with those taking placebo tablets—in their September 28 announcement.
The DSMB recommendation does not apply to the women in the groups using either the tenofovir gel or oral Truvada tablets, or the corresponding placebos; the DSMB recommended that these four study groups continue in VOICE.
“Taken together, the data leave a range of questions on how oral and topical PrEP might be used as a prevention strategy for women,” said Mitchell Warren, executive director of AVAC, a global HIV prevention advocacy group, in a September 28 statement. “One of the most important questions to answer with urgency is which strategies will work for women throughout their lives, and VOICE will continue to be a key trial for answering this question. The different PrEP results we’ve seen in the past year underscore the need for close coordination of clinical trials testing the same or similar strategies and of planning for implementation.”