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Merck AIDS Vaccine Failure May Doom Promising Study
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By John Lauerman
March 24 (Bloomberg) -- A once-promising study of an AIDS vaccine developed by the U.S. will be scaled back and may be scrubbed after the failure of a related Merck & Co. effort.
The vaccine, created by the U.S. National Institutes of Health's Vaccine Research Center in Bethesda, Maryland, may be studied in about only 2,000 people in the U.S. and Africa, rather than 8,500 as had been planned. An international AIDS research group that has helped bring six vaccines to human testing will say today that it has pulled out of the trial.
Support has declined for clinical studies of existing experimental AIDS vaccines since September, when Merck announced its shot may have made people more vulnerable to infection. AIDS researchers say concern was further heightened this month after a second test of Merck's product, conducted in South Africa, found more infections among those vaccinated.
"There isn't a clear understanding of why," said Wayne Koff, senior vice president for research and development for the International AIDS Vaccine Initiative, based in New York. Koff said in an interview that his group told the NIH last week it wouldn't participate in the vaccine trial, called PAVE-100.
"I think we have a safety unknown here," Koff said. His group, which funds and manages AIDS vaccine research, is notifying its affiliated testing sites in Africa that it won't help enroll participants to carry out the U.S. trial.
Opposition to the Trial
More than 33 million people worldwide are infected with HIV, a lethal germ, spread through sex and infected blood, that causes AIDS. While about two dozen AIDS drugs are approved, lifetime treatment costs for each U.S. patient are estimated at almost $619,000, and doctors say a vaccine is essential to preventing new cases. The failure of the Merck shot will set back HIV vaccine research for years, scientists have said.
The AIDS Healthcare Foundation, the Los Angeles-based provider of care and support for about 65,000 patients in 20 countries, called for a moratorium on HIV vaccine research.
"It's unfortunate that it took an AIDS vaccine trial that made more people become infected to make people pay attention and stop this runaway train," said Michael Weinstein, the group's president, in a telephone interview today. "There's no validity in the underlying idea that there will be an AIDS vaccine."
Before spending more money and time on a human test of the government's vaccine, researchers should go back to trying to understand the AIDS virus, said Ronald Desrosiers, a Harvard University scientist.
"I am against seeing it go forward," he said in an e- mail. "I am willing to listen to arguments to the contrary, but have not heard any yet to make me feel otherwise."
`A Post-Merck World'
David Baltimore, a Nobel Prize winner and leading expert on the AIDS virus, told the American Association for the Advancement of Science meeting in Boston last month that no progress on a vaccine has been made since the disease was discovered 25 years ago.
While AIDS vaccine trials still have merit, for the immediate future, they should be designed to answer questions about how they work, rather than whether they can prevent transmission of the virus, Mitchell Warren, executive director of the New York-based AIDS Vaccine Advocacy Coalition, said in a telephone interview last week.
"We're living in a post-Merck world and we're going to have to ask questions in a different way and operate in a different reality," he said. Merck officials declined to comment on the U.S. study.
Recruitment Challenges
The U.S. vaccine, referred to as the VRC vaccine for the center where it was developed, has at least two features in common with Merck's. Both aim to arouse immune defenders called T-cells against HIV, and both contain a cold virus called adenovirus-5.
In the Merck study, vaccinated men were at increased risk of HIV if they started the study with a high level of immunity to the cold virus, meaning they previously had been exposed to the virus. Researchers saw the same pattern in early results of an African test of the Merck vaccine, which was also halted last year on safety concerns.
No one with high levels of immunity to adenovirus-5 will be enrolled in the government vaccine trial, called PAVE-100, should it proceed, said Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, part of the NIH. That may rule out nine of 10 of potential participants in Africa, where levels of infection with the adenovirus are much higher than in the U.S, Koff said. A requirement that men in the study be circumcised, rare in some African communities, would also complicate recruitment, he said.
"We were convinced that we would have a difficult time enrolling significant numbers of individuals," Koff said.
`Something to Learn'
The government vaccine contains additional elements that might make it more effective than Merck's, said Warren of the AIDS Vaccine Advocacy Coalition. It uses DNA that researchers hope will induce human cells to make vaccine-like proteins, which in turn will generate a protective immune response. The cold virus in the vaccine is also hoped to provoke a stronger immune response than Merck's shot did, he said.
"It's a different product," he said. "There's certainly something to learn by advancing PAVE-100."
Koff's group had planned to assist in studying the government's vaccine in about 1,000 people in Africa. Finding participants who would have to be circumcised and lacking immunity to the infection-linked cold virus may be difficult. Human studies of AIDS vaccines should probably be kept small and aimed at discovering how to design better shots than the current crop, Koff said.
Research Summit
"Most of the information from these studies will feed into discovery, unless we were to be surprised in a positive way," he said.
NIAID, the U.S. infectious-disease agency, is holding a meeting tomorrow with AIDS researchers from across the country to review its $497-million AIDS vaccine research program, including the "balance" of human trials against laboratory research. An earlier-scheduled meeting to discuss the government's vaccine test was postponed in February until after the vaccine summit.
"In every organization, it's useful to stop and take stock, particularly when you've had an unanticipated result," said Bruce Walker, a Harvard Medical School AIDS researcher who's coordinating studies to determine what happened in the Merck shot's trial. "That's what this is about."
To contact the reporter on this story: John Lauerman in Boston at jlauerman@bloomberg.net.
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