New Vaccine Shows Promise for Preventing HIV

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.”

According to the Centers for Disease Control and Prevention’s HIV/AIDS Surveillance Report for 2007, >100 million people in the United States have been diagnosed with the disease. The first cases of AIDS were reported in 1981, and by the end of 2007, an estimated 455,636 people in the 50 states and the District of Columbia were living with AIDS. From 2004 through 2007, the total number of new cases of HIV/AIDS increased 15% in the 34 states included in the report, but this increase was attributed to changes in state reporting regulations and increases in HIV testing.

IAVI officials said that even if the trial results do not lead directly to a vaccine, they at least provide researchers with a platform on which to improve and to validate animal models and assays and a way to attract investment and energy to the research and development of an AIDS vaccine. The outcome also demonstrates the importance of testing AIDS vaccine candidates in human trials. “Because HIV causes AIDS only in humans, we can only learn so much from animal models,” Mr. Berkley added. “We could not have learned what this study is going to teach us any way other than through clinical research, and we expect to learn a great deal.”

Collaborating partners on this study included the US Army, the Thai Ministry of Public Health, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, Sanofi Pasteur, and GSID. The collaborators are working with external experts to determine the need for additional studies on this vaccine regimen and consider the impact of this study’s findings on other HIV vaccine candidates.

Officials from the World Health Organization and the Joint United Nations Program on HIV/AIDS are optimistic about the results, but said that licensure of the vaccine may not be possible solely on the basis of results from the Thailand study. The vaccine components in this particular regimen have not been proven to be effective in other parts of the world with diverse host genetic backgrounds and different HIV subtypes driving different regional subepidemics. In addition, early HIV vaccines with modest levels of efficacy would most likely have to be used as complementary tools in combination with strategies to promote changes in behavior.—Charles Boersig