Large Trial Finds AIDSVAX Vaccine Fails to Stop Infection

By Andrew Pollack and Lawrence Altman
The New York Times

The first AIDS vaccine ever to be tested in a large number of people has failed, over all, to protect them from infection with the virus that causes the disease, the company that makes it, VaxGen, said today.

The vaccine did, however, seem to significantly lower the infection rate among African-Americans and other non-Hispanic minorities participating in the trial, the company said.

Its researchers called this finding totally unexpected and said they were at a loss to explain why there would be ethnic differences in response to the vaccine. They conceded that the findings, though statistically significant, might change if the vaccine were tested among more members of minorities, who were only a small fraction of the people in the trial.

We're skeptical about the small numbers," said Dr. Donald N. Forthal, chief of infectious diseases at the University of California at Irvine and one of the investigators in the trial. "On the other hand, this is a very intriguing finding."

The findings suggest that the vaccine failed in its prime objective. The vaccine showed virtually no effectiveness over all, making it extremely unlikely that it could be approved for use without further trials. But the data offer clues to possibly productive avenues of research.

Dr. José Esparza, the leading vaccine expert at the United Nations AIDS agency in Geneva, said he was very encouraged by the results.

"This is the first demonstration of protection in humans, and one of the most significant findings in H.I.V. vaccine research in many years," Dr. Esparza said. Though the vaccine is "not the final product that we need for public health use" and is not ready to be licensed for sale, he said, it "should give encouragement to all vaccine developers."

Dr. Esparza said it was imperative to conduct more vaccine trials, especially in Africa.

VaxGen, a small biotechnology company here, was formed to carry the vaccine forward after the National Institutes of Health and the company that invented the vaccine, Genentech, decided it was not worthy of clinical trials.

The fact that the vaccine advanced to such large trials was largely the result of the doggedness of the company co-founder and president, Dr. Donald P. Francis, an epidemiologist and virologist who formerly worked at the Centers for Disease Control and Prevention, where he was one of the first experts to see the dangers of AIDS when the disease became known more than 20 years ago.

The vaccine, known as Aidsvax, is made from a protein called gp120, the same protein that protrudes from the surface of H.I.V. and helps the virus dock with cells of the body's immune system. The protein in the vaccine is made in genetically engineered hamster ovary cells. Since the vaccine consists of only one protein and not the whole virus, it cannot give someone AIDS. But it is designed to provoke the immune system into making antibodies that will latch on to the gp120 protein in the real virus and the virus from infecting immune cells.

Most mainstream AIDS researchers have said they do not believe the approach will succeed. For one thing, HIV mutates rapidly and there are a number of subtypes of of the virus, which themselves may have many different strains. VaxGen's vaccine is designed to elicit antibodies to only two strains of subtype B, the type most prevalent in North America and Europe.

Even VaxGen said it was hoping its vaccine would prevent 30 percent of infections, which is far lower than for most vaccines, but could have been enough for approval. But even that level was not attained.

Many scientists now say a more effective vaccine approach would be to spur a second arm of the immune system, the so-called killer T cells, to destroy cells infected by the AIDS virus.

These and other newer vaccines are under development, but they are all several years behind Aidsvax. Because Aidsvax was the first to be tested in a so-called Phase 3 clinical trial, usually the final testing stage for marketing approval, interest in the results has been intense.

The trial took place at 59 sites, mostly in the continental United States, with some in Canada, Puerto Rico and the Netherlands. It involved 5,400 volunteers, mostly men, none of whom were infected with H.I.V. at the start of the trial.

About 5,100 of the participants were gay men who said they had had sex with many other men. The other 300 were women who were considered at high risk of infection through sexual contact.

GMHC Criticizes VaxGen for Obfuscation of Trial Results of Its AIDS Vaccine

Gay Men's Health Crisis (GMHC), the nation's oldest AIDS service organization, today criticized VaxGen, the maker of the AIDS vaccine candidate, AIDSVAX, for obfuscation of its trial results. Despite showing no effect overall in protecting against infection with HIV, the company highlighted a subset of results which seemed to show efficacy in African-Americans and Asians.

GMHC looks forward to the day when HIV will be a preventable disease and is a strong supporter of AIDS vaccine research, including VaxGen's research efforts. However, the conduct of vaccine research must be held to the highest standards of ethics and accuracy, as millions of lives depend on the results of these scientific studies.

"Subset analyses are problematic in the best of cases. With small numbers of African-Americans and Asians in the trial and wide confidence intervals associated with the results, making any statements about efficacy in this subpopulation is grossly premature," said Gregg Gonsalves, Director of Treatment and Prevention Advocacy at GMHC. VaxGen's assertions of its vaccine's efficacy among blacks are based on 13 infections in this population in a trial of more than 5000 participants. The assertions about efficacy among Asians are based on only 4 HIV infections in the study.

GMHC is particularly worried that the "spin" of these results will sow confusion in communities particularly at risk in the United States, specifically African-Americans. "VaxGen has not proven that this vaccine is effective among African-Americans or Asians, yet preliminary press reports are claiming that this may be the case," said Ana Oliveira, GMHC's Executive Director. GMHC is asking the company to clarify its statements on the subset analysis of African-Americans and Asians, particularly its claims of efficacy for this population, and is calling on the media to look more closely at the data before drawing any conclusions.

GMHC also has concerns that VaxGen's interpretation of its results will also provide false hopes in Africa and Asia, where the rates of HIV infection are highest in the world, and which will be the major market for AIDS vaccines. It is important to note that the vaccine in this study did not use strains of HIV prevalent in Africa and Asia.

GMHC fears that claims of partial protection for African-Americans and Asians, by extension, could imply that Africans and Asians living outside of the United States could see some protection from this vaccine. GMHC is urging the company not to overstate the promise of its product based on scant and inconclusive data.

02/25/03

Sources
- A Pollack and L Altman. Large Trial Finds AIDS Vaccine Fails to Stop Infection. The New York Times. February 24, 2003.
- Gay Men's Health Crisis. GMHC Criticizes VaxGen for Obfuscation of Trial Results of Its AIDS. Press Release. February 24, 2003.