In a puzzling and potentially troubling development, an AIDS vaccine tested in a closely watched trial might have increased the risk among vaccine recipients of becoming infected with HIV, researchers reported Wednesday at a scientific meeting in Seattle.
But the researchers said not enough data existed to determine what the findings mean about the vaccine, which is made by Merck.
The increased risk was principally among a group of people who had pre-existing levels of immunity to a common cold virus known as adenovirus type 5, which was modified to become a critical part of the vaccine. Researchers emphasized that the vaccine itself could not cause AIDS, but one theory is that the cold virus may have activated the immune system in some way to make certain recipients more susceptible to HIV infection when exposed to the virus that causes AIDS.
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But participants at the meeting also emphasized that the findings could be a statistical fluke and that non-biological factors might have accounted for the difference. Examples of such factors are rates of circumcision and sexual practices among trial participants.
In late September, Merck unexpectedly halted the trial of its experimental HIV vaccine because it failed in its two main objectives: to prevent infection and to lower the amount of HIV in the blood among those who became infected.
3,000 volunteers in test
The vaccine was being tested among 3,000 volunteers at high risk of developing AIDS in nine countries, including the United States. Merck’s was seen as one of the most promising experimental AIDS vaccines to have been tested on people. Many scientists and AIDS advocates have called the failure of the experimental vaccine a major setback.
“The new analyses are both disappointing and puzzling” because they offer no explanation for the vaccine’s failure, said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, a partner in the vaccine trial.
In September, a preliminary analysis of about half those in the trial suggested that those vaccinated were becoming infected at roughly the same rate as those receiving a placebo. There were 24 HIV infections among those vaccinated compared with 21 who received a placebo.
But the new analysis looked at all the trial participants and found a wider difference — 49 in the vaccinated group compared with 33 in the placebo group. Further analysis showed that the imbalance was much more apparent among those who had the highest level of pre-existing immunity to the cold virus used in the vaccine.
Among 778 male volunteers who had a high level of pre-existing adenovirus immunity, 21 of those receiving the vaccine developed HIV infections compared with nine in the placebo group. Researchers told reporters that when such an analysis is performed after a trial is stopped, defining what is statistically significant is difficult.
The difference between the groups with low levels of adenovirus immunity was smaller: 28 among the vaccine recipients compared with 24 who received a placebo. That difference was not statistically significant.
Verifying the hypothesis requires extensive laboratory tests.
Testing could take years
Findings could determine the underlying biological mechanism responsible for the vaccine’s failure. It will take months to years for such tests to be completed, Keith Gottesdiener, a Merck vice president, said in an interview.
Although 35 percent to 40 percent of the trial participants were women, only one woman became infected with HIV. The reason for the gender difference is unknown. Her case was removed from the statistical analysis.
The new reports create even more scientific confusion about how to develop a vaccine to stop the global HIV pandemic, which has infected an estimated 39 million people and killed 25 million more. The findings raise questions about whether adenovirus can ever be used as a crucial ingredient in an AIDS vaccine and whether new tacks will be needed. Use of a modified virus as a vector to deliver HIV genes is a new and evolving way to make an AIDS vaccine. The Merck vaccine included three synthetic HIV genes.
Scientists and AIDS advocacy groups said the vaccine failure should not lessen the commitment to develop an AIDS vaccine.
The new data “raise more questions than answers for the field of AIDS vaccine,” the AIDS Vaccine Advocacy Coalition, a non-profit community- and consumer-based group, said in a statement.
The coalition urged AIDS scientists not to begin trials of other new vaccines until more definitive conclusions could be reached from further analysis of the Merck vaccine.
“We did a beautiful experiment, but it definitely was a disappointment,” Larry Corey of the University of Washington, who led the investigators, said.
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Cold virus plays role
*The vaccine is made from a common cold virus with three synthetic HIV genes tucked inside. It’s designed to stimulate the immune system to kill any HIV-infected cells encountered in the future.
*The problem researchers encountered was that volunteers with pre-existing immunity to that cold virus were much more likely to get infected with HIV if they got the AIDS vaccine than if they got the dummy shot.
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*The question is whether the infection rate is related to the vaccine, to other factors or to coincidence.
— Associated Press