February 25, 2003
Official Hopes to Explain AIDS Vaccine Disparities
top federal researcher expressed hope yesterday that the tests that his
agency was planning would explain why the first large-scale trial of an AIDS
vaccine had found it more effective among African-Americans and other
non-Hispanic minorities than others.
The researcher, Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, said his institute planned to perform an array of laboratory tests on blood samples to uncover any possible immune or genetic factor that might account for the findings.
But Dr. Fauci said he would first consult a number of statisticians to
try to determine whether the possible protective benefits among minorities
from the vaccine — known as Aidsvax and manufactured by
The study involved 5,400 participants, mostly in the United States, and failed over all to protect them from infection with the AIDS virus. The possible benefit involved a small subset of nearly 500 minority participants and was an unexpected finding.
"The statistics look impressive," Dr. Fauci said.
But Dr. Fauci and other AIDS and vaccine experts interviewed urged caution, stressing that the possible benefit was based on preliminary statistical analyses.
VaxGen officials received the data on Feb. 15 from an independent committee that oversaw the integrity of the trial. VaxGen will need additional weeks to analyze the findings before scientists can better determine the significance.
One reason for caution, said Dr. Steven G. Self, a statistician at the University of Washington in Seattle, is that the figures from subsets in trials with negative overall findings can be misleading. Such findings often generate the hypotheses that scientists test in additional studies. Dr. Self said VaxGen might be able to test such hypotheses in the second part of its study, being conducted in Thailand and due to be completed this year.
Dr. Fauci said that the findings were "provocative enough to give very good reason to consider funding a larger study of this or other AIDS vaccines among minorities," if statisticians agree that they would be worthwhile.
Dr. Fauci said his team would test cells in the blood of participants for specific HLA antigens, which can indicate whether a person is more susceptible to certain infections or less likely to respond to certain vaccines. He said they would also test the cells to see how they responded after being exposed to components of viruses. VaxGen researchers also said they would study vaccine recipients' blood samples and compare antibodies from infected test subjects with antibodies of subjects who remained free of the virus.
The researchers hope to identify which antibodies actually protect against infection, rather than simply signaling that infection has occurred. The identification of such antibodies, known as correlates of immunity, might greatly help vaccine development.
The trial grew out of a decision in 1994 by the allergy and disease institute not to support a big clinical trial of the vaccine, leaving the work to VaxGen. Yesterday, Dr. Fauci congratulated VaxGen for conducting a good study that would be "a major contribution" to the search for an effective AIDS vaccine.
The Gay Men's Health Crisis of New York accused VaxGen of making statements about the effectiveness of Aidsvax that obfuscated its trial results.
"Making any statements about efficacy in this subpopulation is grossly premature," said Gregg Gonsalves, director of treatment and prevention advocacy at the gay men's group.
Dr. Thomas Coates, director of the AIDS Research Institute at the University of California at San Francisco, was among the scientists who said the preliminary findings of the trial did not warrant licensing Aidsvax.
The executive director of the Black AIDS Institute, Phill Wilson, said, "However promising this vaccine may look for black people, it is a promise for tomorrow."
"The possibility of a vaccine that works only for African-Americans should jump-start black America's involvement in the vaccine development and approval process," Mr. Wilson said as he and 1,000 participants in the institute's fifth annual national conference on African-Americans and AIDS in Manhattan emphasized the need for more blacks to be informed, tested and, if found infected, treated.
The World Health Organization and the United Nations AIDS program said there was an urgent need for additional research to learn why Aidsvax seemed to work just for minorities.
Dr. José Esparza, the top AIDS vaccine expert for the United Nations, said it was important for scientists to learn whether the different responses to the vaccine were a result of ethnicity alone or differences in behavior patterns in ethnic groups.
"We have to answer the questions," Dr. Esparza said. "Why only in blacks? Would this vaccine work in Africa?"
Dr. Esparza said there was a precedent for experimental vaccines that show effectiveness in particular subgroups. He cited the example of an experimental herpes vaccine that showed protection just in women in a recent study.
"We still do not have an explanation for that," he said.
About an H.I.V. vaccine, Dr. Esparza said, "we cannot take the wrong tack, believing this is just racial, when in fact it could be something else, and we have not identified it yet."
Dr. Nils Daulaire, president and chief executive of the Global Health Council, said that although the VaxGen findings were "a blow to our hopes for turning the tide of AIDS in the near future, they will help researchers to identify more promising avenues toward a highly effective, globally available AIDS vaccine."