Cath Lab Digest

First to Demonstrate Some Effectiveness in Humans

Since the emergence of the human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) >25 years ago, there have been significant advances in testing for and treating the disease, as well as massive educational campaigns to encourage prevention. Despite these efforts, along with improved treatment with combination antiretroviral drug regimens, the number of cases continues to grow. Researchers have been mostly unsuccessful in developing a vaccine to prevent the spread of HIV/AIDS, but the US Military HIV Research Program and the Thai Ministry of Public Health recently announced positive results from a phase 3 clinical trial involving a prime-boost combination of 2 AIDS vaccine candidates that was partially effective at preventing infection with HIV.

Conducted in Thailand and referred to as RV144, the trial tested a prime-boost vaccine strategy that combined 2 vaccines based on strains of HIV that circulate in Thailand. The first, or prime, vaccine, known as ALVAC HIV, was developed by Sanofi Pasteur, and the booster vaccine, AIDSVAX B/E, was originally developed by VaxGen and is now licensed to Global Solutions for Infectious Diseases (GSID). The proof-of-concept study, which began in 2003, was designed to evaluate the vaccine strategy’s ability to prevent HIV infection, as well as its ability to reduce the amount of HIV in the blood of those who became infected after they enrolled in the study.

Investigators recruited >60,000 interested participants, screened 26,675 people to see if they met the entry criteria, and enrolled 16,402 HIV-negative men and women between the ages of 18 and 30. Half of the participants received the prime-boost vaccine regimen and half received placebo. Volunteers received vaccinations over the course of 6 months and were followed for an additional 3 years. Before agreeing to participate, all volunteers were informed of the potential risks associated with receiving the experimental vaccine regimen used in this study and consented to participate in the study. Volunteers continued to receive an HIV test every 6 months for 3 years following vaccination and were counseled on how to prevent becoming infected with HIV.

According to final results released by the trial sponsor, the US Army Surgeon General, the prime-boost combination of ALVAC HIV and AIDSVAX B/E lowered the rate of HIV infection by 31.2% compared with placebo. No vaccine safety issues were observed in the trial.

In the final analysis, 74 placebo recipients became infected with HIV compared to 51 in the vaccine regimen arm. The efficacy result is statistically significant. The vaccine regimen had no effect on the amount of virus in the blood of volunteers who became HIV-infected during the study. (More detailed results of this study were presented at the AIDS Vaccine Conference, October 19-22 in Paris, France.)

Officials from the International AIDS Vaccine Initiative (IAVI) welcomed the news of positive trial results, calling the vaccine a significant scientific achievement. “It’s the first demonstration that a candidate AIDS vaccine provides benefit in humans,” said Seth Berkley, IAVI president and CEO. “Until now, we’ve had evidence of feasibility for an AIDS vaccine in animal models. Now, we’ve got a vaccine candidate that appears to show a protective effect in humans, albeit partially.”