AIDS Vaccine Conference Kicks Off as Another Study Reports Disappointing Results

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More than 1000 researchers and advocates are convening in Barcelona this week to discuss the latest developments in HIV vaccine research. But study findings published yesterday to coincide with the meeting show that one vaccine candidate thought to be promising -- the DNA/rAd5 prime-boost combination -- offered no protection in the 2500-person NVTN 505 study.

AIDS Vaccine 2013, organized by the Global HIV Vaccine Enterprise and local conference host the HIVACAT Program for HIV Vaccine Research, will feature more than 450 research studies outlining the latest advances and obstacles in the search for an HIV vaccine, according to a conference media advisory. Follow conference news via HIVEnterprise on Facebook or via the hashtag #AIDSVax2013 on Twitter.

One of the major topics of the meeting will be trying to understand the modest protective effect seen in the Thai RV144 trial as well as the lack of efficacy in HVTN 505 and other large trials.

As described in the October 7, 2013, advance online edition of the New England Journal of Medicine and presented at the conference, Scott Hammer from Columbia University and fellow investigators with the HVTN 505 Study Team tested the efficacy of a DNA prime-recombinant adenovirus type 5 boost (DNA/rAd5) vaccine regimen in people at risk for HIV infection in the U.S.

This vaccine regimen includes a primer containing 6 HIV DNA plasmids encoding viral proteins (B Gag, Pol, and Nef and Env proteins from clades A, B, and C) administered at weeks 0, 4, and 8, followed by a booster consisting of an adenovirus 5 vector carrying HIV antigens (clade B Gag-Pol fusion protein and Env glycoproteins from clades A, B, and C) administered at week 24.

The analysis included 2504 men who have sex with men and transgender women at 21 sites. Participants were randomly assigned (1:1) to receive either the DNA/rAd5 vaccine combination or placebo injections.

Results

Based on these findings, the trial's Data and Safety Monitoring Board recommended halting vaccinations due to lack of efficacy in April 2013, at which point approximately two-thirds of the total intended person-years of follow-up had been completed.

"The DNA/rAd5 vaccine regimen did not reduce either the rate of HIV-1 acquisition or the viral-load set point in the population studied," the researchers concluded.

"Thirty years after the discovery of HIV, a safe and effective vaccine is still not in sight," the authors summarized in their sobering discussion. "Of the six efficacy trials that have been conducted to date (including this study), only one, the RV144 Thai trial of ALVAC/gp120, showed protective efficacy."

"Two trials of recombinant bivalent gp120 showed no benefit, and the Step study (HVTN 502) of another Ad5 vector vaccine expressing the internal proteins Gag, Pol, and Nef showed not only futility but an increased early risk of HIV acquisition in men who were uncircumcised or Ad5-seropositive at baseline," they continued.

This study, they wrote, "definitively showed that the DNA/rAd5 vaccine regimen did not reduce either HIV-1 acquisition or the viral-load set point, as compared with placebo."

Trial participant continued to be followed after vaccination was halted. At the first planned updated analysis on September 3, there were 29 infections in the vaccine group and 26 in the placebo group. This convergence of numbers suggests that at least this adenovirus vaccine -- which differs from the one used in Step -- did not increase the risk of HIV acquisition.

"Detailed analyses of the quality and breadth of vaccine-induced immune responses in this study and other efficacy trials will be required to further define these and other correlates of risk," the authors concluded. "Our study gave a definitive, albeit disappointing, result but should provide useful information as newer vaccine regimens and approaches are developed."

The disappointing results of recent vaccine trials stand in contrast to the very encouraging findings on other biomedical prevention methods including oral Truvada pre-exposure prophylaxis (PrEP) and microbicides. Starting in 2014, the separate HIV vaccine and microbicide conferences will be merged into a single meeting, HIV Research for Prevention: Vaccine, Microbicide and ARV-based Prevention Science, to be held for the first time in Cape Town, South Africa, on October 28-31, 2014.

10/7/13

Reference

SM Hammer, ME Sobieszczyk, H Janes, et al (HVTN 505 Study Team). Efficacy Trial of a DNA/rAd5 HIV-1 Preventive Vaccine. New England Journal of Medicine. October 7, 2013 (Epub ahead of print).

Other Source

AIDS Vaccine 2013. Experts to Report on Advances in the Search for the Ultimate HIV Prevention Tool -- a Vaccine -- at AIDS Vaccine 2013. Press release. September 25, 2013.