THURSDAY, Jan. 15, 2004 (HealthDayNews) -- Continuing a U.S. government-sponsored, large-scale trial of an HIV vaccine in Thailand is throwing good money after bad, a team of leading experts claims.
"There is a very weak scientific rationale for going ahead and spending some $119 million and involving thousands of volunteers in this particular vaccine trial," says one of the letter's authors, Dr. Robert W. Doms, chairman of the department of microbiology at the University of Pennsylvania.
The letter from 22 HIV experts, including Dr. Robert Gallo, the co-discoverer of the AIDS virus, appears in the Jan. 16 issue of Science.
The trial is now in what is known as phase III, which tests if a drug works in large groups of several hundred to several thousand people. The trial is designed to compare the test drug to other standard or experimental drugs. During the trial, adverse events and data on safe uses are also collected. A phase III trial is the last step before a drug can be approved for regular use.
One of the components of the vaccine called gp120, which has completed phase III trials, "failed completely in providing any degree of protection to HIV infection," Doms says.
The other component, called ALVAC, has had unimpressive results in trials, he adds. "Combining something that's failed with something that has not been terribly impressive doesn't seem to provide a good rationale for proceeding with such a large and costly trial," Doms says.
Gp120 is made by VaxGen, and ALVAC is a product of the pharmaceutical giant Aventis Pasteur.
The U.S. government defends the trial, saying this combination has not been tested on humans before now and it should at least be attempted. In a statement, the National Institute of Allergy and Infectious Diseases (NIAID), an arm of the National Institutes of Health (NIH), says the scientists have provided "no evidentiary data" that the trial will fail.
The NIAID and the U.S. Army Medical Research and Materiel Command, which are co-sponsoring the trial, say they plan to publish a rebuttal to the letter in an upcoming issue of Science.
Doms believes that money for this trial would be better spent on other vaccines that are in early development, but that show greater promise.
Another of the letter's authors, Dr. Dennis R. Burton, a professor of immunology at The Scripps Research Institute, agrees that other trials being planned show more promise.
The failed gp120 trials were based on the vaccine creating antibodies to HIV, but the vaccine did not create these antibodies, Burton says.
Burton believes that vaccines that create T-cell responses may be a better approach to creating an effective HIV vaccine. "A T-cell vaccine might not be enough, but the concept should be tested," he adds.
It is particularly difficult to develop an HIV vaccine, since the virus mutates very quickly, Burton says.
"Every time you come up with some way of containing it, the virus finds a way round the protective mechanism you have come up with. There are more different strains of HIV in a single person than there are strains of flu in the whole world," he says.
Burton says that the ultimate answer to an HIV vaccine will probably be a combination vaccine that creates antigens and T-cell responses. But this is a slow process, and such a vaccine will probably take years to develop and test.
Last year, the HIV Vaccine Trials Network (HVTN), which represents the largest group of doctors and researchers, canceled a similar trial, because the earlier phase I and phase II trials had found ALVEC to be ineffective, Doms notes.
Doms adds that NIH is directing more of its budget to purchasing anthrax vaccine and into bio-defense. "Money for HIV research has become tighter, and many of us have seen our own research grants being cut."
When the trial was first planned it may have been reasonable, but the "scientific landscape has changed, and I do not feel it is reasonable now," Doms says.
Dr. Paul Spearman, the co-principal investigator of the Vanderbilt HIV Vaccine Program at Vanderbilt University, did not sign the letter but agrees with it.
"The bulk of scientific data in the field strongly argues against a chance for efficacy of this vaccine combination, and an informed decision to halt the progression to phase III testing should be made," Spearman says.
"Instead, we should await the newer generations of vaccines that are currently in phase I and phase II testing which have a much greater potential for efficacy," he adds.
That isn't true, according to the sponsors. "In combination, these vaccines induce a repertoire of immune responses quantitatively and qualitatively different from those induced by either component alone," the NIAID statement says.
Dr. Jonathan N. Weber, a clinical professor of medicine and principal investigator of the HIV Research Group at Imperial College in London, says that he shares "the view that the ALVAC/gp120 phase III trial in Thailand is not justified on scientific grounds. I disagree that the previous phase III trials of gp120 was fully predicable, and hence not justified."
The negative results of the previous trial, "while miserable for the field and for global public health, nonetheless have moved the science forward with confidence," Weber says. "The result is what allows us to state that the ALVAC/gp120 trial is doomed to failure because of poor immunogenicity of ALVAC, and proven lack of activity of gp120," he adds.
The first two phases "determined that the strategy was safe and induced immune responses meeting pre-defined and thoroughly-vetted milestones," the NIAID statement says. "No laboratory tests or animal models have been demonstrated to predict HIV vaccine efficacy in humans. Thus, only human trials can determine efficacy."
Officials with VaxGen declined to comment. Lisabeth Bull, a spokeswoman for HVTN, also declined to comment.