Wall Street Journal - September 25, 2009
Gautam Naik

The first vaccine to show any sign of preventing the spread of HIV has provided the most encouragement since the 1990s in the three-decades quest to stem the global AIDS epidemic.

Results of a trial involving more than 16,000 adults in Thailand indicate the vaccine regimen was safe and reduced by 31% the chance of infection with the AIDS-causing human immunodeficiency virus, or HIV, according to the U.S. National Institutes of Health, which helped fund the study.

Though that 31% is modest, it has heartened public-health experts and scientists. It is the first time a vaccine has been shown to confer any HIV protection at all. Should this prove to be a forerunner to a usable vaccine, it would be the second big game-changer in AIDS research since the mid-1990s, when potent new "drug cocktails" -- a mix of protease inhibitors and other anti-retrovirals -- turned AIDS from a virtual death sentence into a chronic but manageable disease for many patients.

"Anti-retrovirals are obviously a very important tool against AIDS, but preventing infections is the highest priority," said Saladin Osmanov, coordinator of the HIV-vaccine initiative overseen by the World Health Organization and UNAIDS, an arm of the United Nations. "The results from Thailand are modest, but they're a very good start" toward a vaccine.

The surprisingly good data from Thailand could reignite an old debate about how to respond to AIDS globally: Put more money and resources into prevention with vaccines, or focus more on drugs that prolong the lives of those already infected.

About 33 million people were living with HIV world-wide in 2007, the most recent year for which statistics were available, according to the U.N. That same year, about two million people died of AIDS and 2.7 million more became infected.

For now, the scientists will try to figure out why the latest vaccine worked when previous ones failed, and why it worked for some participants and not others. They also need to understand how long the vaccine's protection lasts and whether its efficacy can be boosted beyond 31%.

"This is the beginning of the effort," said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which is part of the NIH. "It has opened up a door for us to ask some very important fundamental science questions as well as some clinical questions."

In the three-year experiment, 74 of 8,198 people who received placebo shots became infected with HIV compared with 51 of 8,197 people who received the vaccine, suggesting the vaccine regimen could have reduced the risk of being infected by 31%.

The NIH said the results are statistically significant. However, researchers involved in the trial haven't yet publicly released any detailed data. Vital details are expected to be presented at an AIDS-vaccine conference in Paris next month.

The regimen consists of two vaccines. One is a primer dose made by Sanofi Pasteur, a division of Sanofi-Aventis SA of France. The other is a booster dose developed by Vaxgen Inc. and now licensed to Global Solutions for Infectious Diseases, of South San Francisco, Calif.

"It's unclear why two vaccines that have been separately tested and had little activity or none, when put together seem to give 30% protection," said Barry Bloom, former dean of the Harvard School of Public Health. "That's a puzzlement."

The idea of combining two vaccines to bolster the breadth and potency of an immune response is an old one. Such combinations had worked in animal models in the 1990s, when Sanofi combined its HIV vaccine with a booster. The decision to try this in the Thai trial was made by the key partners, including Sanofi Pasteur, the U.S. Army, the NIH and VaxGen, according to Jim Tartaglia, vice president of R&D at Sanofi Pasteur.

The vaccine was specially designed for use in Thailand because it is based on the subtype B and E strains of HIV common there. Thus, it isn't clear whether it would work in Africa, where subtypes A, C and D predominate. Two-thirds of the 33 million people with HIV live in Africa, and 75% of all AIDS deaths in 2007 occurred there. One way around the problem is to test an Africa-specific vaccine incorporating local HIV subtypes.

The U.S. Army's involvement in a vaccine trial isn't unusual. On its Web site, the U.S. Military HIV Research Program notes that its researchers have often been involved in finding fixes for infectious diseases that affect American forces. "HIV continues to pose a significant and persistent threat in terms of readiness and force protection, and may affect the stability and security of many nation-states," it reads.

There were low expectations for the Thai trial, largely due to the dismal track record. There have been more than 100 vaccine trials since 1987; one of the biggest setbacks occurred in 2007, when Merck & Co. ended a closely watched trial.

The Thai trial was set up to see not only whether the vaccine could prevent infections but also whether it could lower the viral load which, in turn, has an effect on how the disease progresses. However, vaccinated patients who still became infected didn't have lower levels of the HIV virus than patients who received the placebo and became infected.

Dr. Supachai Reks-Gnarm, principal investigator of the Phase III HIV vaccine trial, speaks in Bangkok.

Cate Hankins, chief scientific adviser at UNAIDS, noted that only 125 people who participated in the trial ended up with HIV and said a larger sample might have revealed different results about viral loads.

The trial enrolled men and women 18 to 30 years old drawn from the general population, at various levels of HIV risk. Those who contracted the virus have been provided with medical care and treatment. The trial was sponsored by the U.S. Army and conducted by the Thailand Ministry of Public Health, collaborating with NIAID, Sanofi Pasteur, GSID and others.

- Ron Winslow and Jacob Goldstein contributed to this article. Write to Gautam Naik at gautam.naik@wsj.com

Corrections & Amplifications:

During a recent trial of an AIDS vaccine in Thailand, 16,402 volunteers participated in the study; 135 of them were infected with HIV. A graphic with this article incorrectly stated 125 people were infected.

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