HVTN 505 Expanded to See if Vaccine Candidate Can Block HIV Acquisition

By Regina McEnery

A Phase II AIDS vaccine trial known as HVTN 505 will expand enrollment to determine whether two vaccine candidates administered sequentially in a prime-boost regimen are capable of protecting against HIV infection. The two candidates—a DNA-based vaccine and a candidate that employs an inactivated strain of the commonly circulating cold virus adenovirus serotype 5 (Ad5)—were developed by the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases (NIAID).

The HVTN 505 trial, which was launched in 2009, was initially designed to determine whether individuals who become HIV infected through natural exposure, despite vaccination, have lower viral loads (the quantity of HIV circulating in blood) than those who receive placebo (see VAX July 2009, Global News). With only this endpoint, the trial was slated to enroll 1,350 circumcised men or transgendered women who have sex with men. Adding protection against infection as an additional endpoint requires expanding enrollment to 2,200 volunteers, who will be enrolled at 21 sites in 18 US cities. So far, investigators have enrolled 1,344 volunteers and are on track to enroll the remaining volunteers by mid-2012, according to Scott Hammer, principal investigator of the HVTN 505 trial.

Carl Dieffenbach, director of the Division of AIDS (DAIDS) at NIAID, says the expanded trial is a positive step for the field, but he cautioned observers to keep the scope of the trial and where it might lead in perspective. “We have to be careful that we continue to put this forward without trying to over-promise,” he says.

One Oral PrEP Arm Discontinued Early in VOICE Trial

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 VAXJuly 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).