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AIDS Vaccine Testing at Crossroads After Little Progress in 25 Years, Scientists Urge Return to Basic Research
  By David Brown
Washington Post Staff Writer
Wednesday, March 26, 2008; Page A04
The leaders of the federal government's effort to develop an AIDS vaccine said yesterday that more of their budget needs to be spent on basic lab research and less on testing the current crop of vaccines, none of which has proved useful in human trials.
The declaration made at a "summit meeting" is tantamount to an admission that almost no progress has been made in the search for an AIDS vaccine in the past 25 years and that something close to new start is necessary.
The conference, held at the National Institutes of Health in Bethesda, was called after a much-touted vaccine tested in half a dozen countries not only failed to benefit people who received it but also may have actually increased their chance of becoming infected with HIV, the virus that causes AIDS.
"We need to turn the knob toward [basic scientific] discovery -- nobody should be unclear about that," said Anthony S. Fauci, head of the National Institute of Allergy and Infectious Diseases.
One of the co-chairmen of the meeting, Warner C. Greene of the University of California at San Francisco, was more definitive in his assessment. "There is no question the AIDS vaccine enterprise is in need of a major mid-course correction," he told the gathering of about 300 scientists, who came from as far away as South Africa and Kenya for the one-day meeting.
Carl W. Dieffenbach, the head of the NIH's Division of AIDS, acknowledged that "this summit does mark a change in our approach."
The meeting was called after two studies testing the same vaccine were stopped in September. The vaccine, made by the pharmaceutical giant Merck, used a crippled version of a common respiratory virus, called adenovirus type 5, to deliver a selection of HIV proteins to the immune system in the hope of inducing protection.
The studies were stopped when early results suggested that people receiving the vaccine were more likely to become infected with HIV than people receiving placebo injections. The reason is unknown and the subject of intensive scientific study.
NIH is spending $497 million on AIDS vaccine research this year, with about $476 million going to researchers outside its campus. About 47 percent of the money funds basic research and 38 percent funds testing "candidate vaccines" in humans. Fauci said the ratio needs to be tipped more steeply in favor of basic research.
Although researchers have tested numerous AIDS vaccines on small groups of volunteers, only three vaccines have gone to large clinical trials with thousands of volunteers.
Earlier this decade, one product, called AIDSVAX, was found to be ineffective. The Merck vaccine, which showed promising results in monkeys, may have been harmful. A third vaccine, being tested in an experiment nearing completion in Thailand, is given little hope of working by most researchers, 21 of whom wrote a letter to the journal Science several years ago saying that the study should not even begin.
The search for an AIDS vaccine has proved difficult for several reasons.
Successful vaccines mimic the protection the body normally provides when confronted with a virus, bacterium or other microbe. HIV, however, mainly attacks immune system cells, which are the ones a vaccine is trying to enlist for help.
Furthermore, unlike most viruses, HIV stitches itself permanently into the DNA of some human cells after entering them. That means that if a vaccine does not provide full protection within days -- and possibly even hours -- of exposure, irreversible infection occurs.
A few people who become infected with HIV are able to survive without treatment indefinitely -- so-called elite controllers. Many non-human primates also tolerate the monkey equivalent of HIV without becoming ill. In both cases, how the immune system achieves that outcome is unknown.
"We do not have a vaccine now. . . . We are not only not there, we are not close," said James Hoxie, a researcher at the University of Pennsylvania, who summarized the view of a panel of basic researchers who spoke at the meeting.
One organization yesterday called for the money now spent on AIDS vaccine research to be used for HIV testing, treatment of HIV patients and research on the use of antiretroviral drugs to prevent infection.
"I think we should pull the plug on vaccine research," said Michael Weinstein, president of the AIDS Healthcare Foundation, a private, nonprofit group that provides treatment for people with HIV.
"Do we have any other enterprise that has been studied for 25 years and for which we've spent billions of dollars where we have no results? There's no evidence we'll ever have an AIDS vaccine," he said.
However, Mitchell Warren of the AIDS Vaccine Advocacy Coalition, who attended the meeting, praised it as the beginning of a necessary readjustment of priorities.
"We are at a critical moment in the field. We've had a tremendous setback. But this field is not abandoning the research for a vaccine," he said. "This is not the end of the line for AIDS vaccine research. That was an important point for everyone."
Several people at the meeting said that they not only support greater spending on basic research, but also that the government must be willing to fund promising, yet unorthodox, proposals, or a generation of young scientists may abandon AIDS research in favor of fields that are less challenging.
Staff writer Rob Stein contributed to this report.
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