One Oral PrEP Arm Discontinued Early in VOICE Trial

By Regina McNery

One arm of a large clinical trial known as VOICE that was designed to test the safety, efficacy, and acceptability of one topical and two oral pre-exposure prophylaxis (PrEP) regimens in more than 5,000 women was discontinued in September after the trial’s independent data safety monitoring board (DSMB) concluded that the study would be unable to show any difference between a daily dose of the antiretroviral pill tenofovir (TDF) and placebo in preventing HIV infection. About 1,000 of the volunteers were randomized to the oral TDF arm. The DSMB found no safety concerns with oral TDF.

Unlike other large-scale PrEP trials that were recently completed or still ongoing, the VOICE study is the first to evaluate both oral and topical PrEP regimens in the same trial. The remaining arms of the trial, which are testing daily administration of the antiretroviral pill Truvada—a combination of TDF and emtricitabine—and the topical administration of a 1% tenofovir microbicide gel will continue in order to determine if they are safe and effective at preventing HIV infection as compared to pill and gel placebo groups.

The US$100 million VOICE trial, which is being conducted at 15 clinical sites in South Africa, Zimbabwe, and Uganda, began in 2009 and is sponsored by the US National Institute of Allergy and Infectious Diseases; the Microbicide Trials Network; Gilead Sciences (the maker of tenofovir and Truvada); and CONRAD, a reproductive health research institute.

The trial is scheduled to conclude in June, at which point investigators will be able to determine whether volunteers in the oral TDF arm were less adherent to the daily PrEP regimen than women in the Truvada or microbicide arms. Michael Chirenje, a principal investigator of the trial in Zimbabwe, says it would be speculation at this point to say what accounted for the failure of oral TDF to show any effect in this trial. “Obviously we are all disappointed and perplexed by the recent results,” says Chirenje. “But in science, we have to accept reality.”

Three other trials have found both oral tenofovir and Truvada to be effective at preventing HIV infection in men who have sex with men and serodiscordant couples—in which one partner is HIV infected and the other is not (see VAX July 2011 Spotlight article, An Antiretroviral Renaissance). However, one trial, known as FEM-PrEP, evaluating oral Truvada in women, was discontinued ahead of schedule after the DSMB concluded that it would be highly unlikely to demonstrate efficacy (see April 18, 2011, IAVI Report blog, Oral PrEP Trial in Women Stopped Early).