Possible AIDS vaccine may have put test volunteers at greater risk than previously reported

A possible AIDS vaccine, which had been tested with great hope and fanfare in Seattle and around the world until halted this fall, may actually have put its volunteers at an even greater risk of developing HIV than previously reported, according to a new report released today.

The latest news is the most emphatic reversal of fortune yet for the so-called STEP Study, a project once heralded as a leading hope for overcoming the global AIDS epidemic. The vaccine had proceeded further into human trials than any other among a new class of possible HIV vaccines.

Researchers in September disclosed that HIV-negative men who received the test vaccine ended up with more cases of infections than men who got placebo injections. Today, the scientists said an analysis of the full data shows that the infection rate among the men who got the would-be vaccine was even higher than initially believed.

What went wrong?

The study was halted in September, more than a year early, because the vaccine wasn't preventing HIV infections, or reducing the amount of virus in the body following an infection. Now researchers are scrambling to figure out whether the vaccine itself may have directly made people more susceptible to infection.

"What is scary is that we're no closer than we've been for a while to the development of an HIV vaccine, which we desperately need globally and locally," said Dr. Bob Wood, director of HIV/AIDS Control Program for Public Health — Seattle & King County. "And if this vaccine actually increased people's risk of acquiring HIV, it might be very difficult to recruit people into future vaccine studies."

The vaccine, developed by the pharmaceutical company Merck, used a disabled form of a common-cold virus to carry three synthetically produced HIV genes into the body. It was hoped that those genes would spur the body to unleash an HIV-targeted immune response using "killer T cells."

Neither the cold virus nor the HIV genes could reproduce, so volunteers could not catch a cold or become infected with HIV directly from the vaccine.

It remains possible that the increased infection rate among test subjects is a coincidence, said Dr. Larry Corey, the lead scientist for the Seattle-based HIV Vaccine Trials Network, which was overseeing the international trials.

At the same time, investigators haven't ruled out the possibility that the vaccine itself might be the culprit, Corey said.

Corey added that other factors, such as circumcision rates and risky behavior among the vaccination group, also could be responsible.

The study included 3,000 men and women between ages 18 and 45 who were considered at high risk of HIV infection. One hundred volunteers were from Seattle; the rest were recruited from 15 U.S. cities and from Canada, Peru, Brazil, Australia, Jamaica, Haiti, Puerto Rico and the Dominican Republic.

Merck co-sponsored the clinical trial along with the Vaccine Trials Network, an international research collaboration based at Fred Hutchinson Cancer Research Center funded by the federal National Institutes of Health.

Releasing information

Volunteers have been notified about the potential increase in infection risk, but they have not been told whether they received the vaccine or placebo. This week, representatives of the trial's co-sponsors are deliberating this week in Seattle about when they should "unblind" the trials and divulge that information.

According to the latest analysis, the men who were particularly susceptible to HIV infection were those who had heightened immunity to the particular cold virus used in the vaccine because of prior exposure.

Among the 392 men with high-immunity who received vaccinations, 21 became HIV infected, compared to 9 cases among the 386 men in the placebo group. The contrast was even greater in the men with the highest levels of immunity, with seven infections among 163 men, compared to two cases among the 157 men in the dummy injection group.

An earlier analysis released in September looked only at the data for subjects with no or low immunity to the cold virus. It found 24 HIV infections among 741 men who received at least one dose of the vaccine. That compared to 21 HIV cases among 762 men in the placebo group. A smaller sample, limited to those who received at least two vaccinations, found 19 HIV infections in the vaccine group and 11 cases in the placebo group.

Those results were enough to cause the researchers to stop the STEP trials Sept. 21.

Kyung Song: 206-464-2423 or ksong@seattletimes.com. Health reporter Carol M. Ostrom contributed to this report.