Failed AIDS vaccine or placebo? Test subjects will learn which they got

An abruptly halted experimental AIDS vaccine trial, managed out of Seattle but tested worldwide, will be "unblinded" so that volunteers potentially put at increased risk for HIV infection can be told if they received the test vaccine or a placebo.

"All we can say for certain at this point is that the vaccine didn't work," said Dr. James Kublin, a lead scientist with the HIV Trials Vaccine Network at the Fred Hutchinson Cancer Research Center. The Seattle trials network coordinates multiple AIDS vaccines trials worldwide for the National Institutes of Health.

One such trial known as the STEP study, involving 100 volunteers in Seattle and a total of 3,000 people in nine countries, was stopped in September when reviewers found evidence indicating that some vaccinated male subjects with high levels of immunity to a cold virus also appeared to have higher rates of HIV infection.

The experimental vaccine, produced by Merck & Co. Inc., uses a disabled cold virus (known as adenovirus type 5) containing three HIV genes that are intended to prompt immunity. It is not yet clear to scientists if, or how, this vaccine might have increased the risk of HIV infection. But those who got the vaccine and had high levels of immunity to the same type of cold virus also had higher rates of HIV infection.

Of 778 male volunteers who had high natural immunity to this strain of cold virus, 21 of those vaccinated became infected with HIV. That was compared with only nine cases of HIV among those who received the placebo. Experts emphasized that the vaccine itself could not have caused the HIV infections.

Kublin worked on a similar trial, called the Phambili study, which was just getting started in South Africa. It was halted at the same time, but the 800 volunteers who had enrolled were told in mid-October if they had received the vaccine.

The decision to similarly inform the STEP study volunteers, he said, was more difficult because of the possibility that unblinding could undermine the ability of scientists to explore how adenovirus immunity might be linked to risk of HIV infection. Researchers, activists and others from all around the world met in Seattle last week to debate and weigh the options.

On Tuesday, the study's oversight committee announced that the volunteers would be told.

"For the AIDS vaccine field overall, this is the best decision," Kublin said.

It's impossible to know if unblinding will hurt further study of these baffling results, he said. But keeping the study blinded risks alienating both current and future AIDS vaccine volunteers.

Scientists will continue to follow all the volunteers, Kublin said, both to monitor their health and to look for clues as to how an individual's adenovirus immunity level might affect the risk of infection from HIV.

"The unfortunate outcome of this study may still provide us with some critical insights," he said.

The fact that this vaccine might have stimulated an immune system reaction, even though in the wrong direction, could still lead to knowledge that may help in the search for an effective AIDS vaccine, Kublin said.