Failure of AIDS Shot Linked to Cold Virus

DAR ES SALAAM, Tanzania, Nov. 7 -- Developers of a failed AIDS vaccine announced Wednesday that it appeared to be ineffective among some people with a preexisting immunity to a virus that causes colds and may have raised their vulnerability to AIDS.

The announcement, made in Seattle, was the latest bad news for a vaccine that only two months ago was regarded as the most promising candidate to slow an epidemic that kills millions of people each year. Trials of the vaccine that involved thousands of participants in the United States, South Africa and other countries were halted in September.

Scientists say the vaccine not only failed to prevent infection with HIV or slow progress of the disease but may have actually increased the HIV risk among trial participants who, by chance, had a preexisting immunity to a common strain of cold virus.

"This is a clinically important finding that we have to address," said Keith Gottesdiener, a vice president for Merck Research Laboratories, which developed the vaccine in conjunction with the National Institutes of Health. He spoke from Seattle, where researchers made the announcement at a scientific conference.

The setback has forced a broad reexamination of the multibillion-dollar search for an AIDS vaccine and raised new questions about when -- or whether -- future experimental vaccines should be tested on humans.

Debate has sharpened in particular over the next major trial of a vaccine, developed by the National Institutes of Health and due to begin human testing in just a few months.

For the Merck vaccine, researchers genetically altered the adenovirus type 5, one of several viruses that cause colds, to include elements of HIV. The goal was to trigger an immune response that would protect a vaccinated person from contracting HIV.

But for reasons scientists do not understand, study subjects with preexisting immunity to adenovirus type 5 apparently became more vulnerable when vaccinated. Among the nearly 800 study subjects with high levels of this immunity, 21 of those who were vaccinated contracted HIV, compared with nine of those who received a placebo.

From a statistical perspective, the numbers were small, but the finding has alarmed vaccine scientists worldwide. The study was shut down Sept. 21 because the vaccine was found to be ineffective.

Researchers say the vaccine did not cause the cases of HIV but may have altered the immune systems of subjects in ways that made some subjects more vulnerable to infection. Analysis of the data is continuing.

"Until we answer some of these questions, we're in a bit of a holding pattern," Mitchell Warren, executive director of the AIDS Vaccine Advocacy Coalition, said in Seattle.

Scientists at the conference were also debating whether to tell each of the study participants, including about 3,000 people in the United States and Latin America, whether they received the placebo or the vaccine, a process called "unblinding" the study.

Gottesdiener said he expected the ethical oversight board to make a decision within the next 10 days.

Researchers in South Africa, who were testing the same vaccine, unblinded their study last month, saying that 801 study participants needed to know if they faced increased risk.

The search for an AIDS vaccine began in the mid-1980s and last year alone cost more than $900 million in private and government funding.