Scientists and community advocates have greeted the results of the AIDSVAX trial, reported here, with strong scepticism about the reported efficacy in Black, Asian and ‘other’ non-White ethnic groups within the trial.
Longstanding VaxGen critics have, predictably, been most outspoken.
John Moore of Cornell University, who is developing a vaccine designed to generate broadly protective neutralising antibodies, suggested that the VaxGen findings were a “statistical fluke” and amounted to “data dredging” by the company.
“If you do this by the signs of the zodiac you’ll find some signs have a better result than other … I doubt there is much to be learned other than the fact the vaccine didn’t work. Everything else is spin control.”
The claimed ethnic differences were biologically implausible: “Antibody responses are not racially driven, so far as I’ve seen,” said Dr Moore.
Gregg Gonsalves, Director of Treatment Prevention Advocacy for GMHC in New York, accuses the company of “obfuscation of trial results”.
“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,” observed Gonsalves. GMHC points out that there were only four infections in the Asian group, which is no basis for drawing any conclusions, and only thirteen in the Black group, which is hardly better.
Expressing concern that false hopes will be raised, especially outside the USA among African and Asian communities affected by viruses very different from those circulating within the USA, GMHC is “urging the company not to overstate the promise of its product based on scant and inconclusive data.”
One reason for scepticism about the biological plausibility of the findings is that the majority of African Americans are, in fact, of mixed genetic heritage. This has been highlighted by some critics of scientific claims about racial differences, such as Dr Paul Stolley, an epidemiologist at the University of Maryland, quoted in the Baltimore Sun: “The likelihood that a vaccine will be effective in certain subgroups and not in the population at large is probably remote, though not impossible.” He called race a “false category, based on skin colour but not on science” especially in the US context.
Dr Robert Gallo, whose Baltimore-based Institute for Human Virology is deeply involved in HIV vaccine research, is also quoted in the Baltimore Sun, drawing attention to the limited range of viruses that gp120-induced antibodies will react with. “This is not a vaccine approach that was based on science,” he said. And on the suggestion it could protect ethnic minorities: “There is no scientific basis for that. I don’t accept it.”
Other scientists and community activists have been more restrained in their criticism of the company’s findings.
Dr Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases, was responsible for the agency's 1994 decision not to proceed with a full-scale efficacy trial of an earlier version of AIDSVAX. He is quoted by the New York Times as saying that his agency will work with the company on a thorough evaluation of stored blood samples, including a look at possible genetic factors influencing immune responses (HLA diversity). He stressed the need for closer examination of the findings, to look for differences other than race between the groups in which there was apparent protection and the majority among whom there was none.
Dr Steven Self, of the University of Washington in Seattle, a statistician who heads a group working on trial design for the HIV Vaccine Trials Network, observes that subset analyses of this kind must always be treated with great caution. The proper way to view them is as leads for further investigation, which must be confirmed by larger studies.
The trial “simply was not designed to demonstrate efficacy in this subgroup,” said Chris Collins, executive director of the AIDS Vaccine Advocacy Coalition.
Martin Delaney of Project Inform in San Francisco considers that “it would do a great deal of harm to stir up hopes for selected groups over a vaccine that has proven so ineffective overall.”
Regardless of the biological validity of race as a category in the USA, it is clear that as a social category African-Americans are being affected more heavily by HIV than any other section of the population.
VaxGen has observed that if they failed to follow up and investigate the possibility their product could help stem the epidemic, they would be “slaughtered” for abandoning people who need better means of HIV prevention.
This position has also been supported by some of the trial physicians, such as Neil Flynn of UC Davis: “Half of all new HIV infections [in the USA] are in African Americans. We have to push forward.”
Phill Wilson, Executive Director of the Black AIDS Institute, observed that “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.” His institute has just held its fifth annual national conference in New York, attended by 1,000 participants, pushing for greater AIDS awareness and access to testing and treatment among US minority populations.
The second VaxGen trial, of AIDSVAX B/E in Thailand, will clearly be an important opportunity to confirm – or help disprove – the possibility that their vaccine approach can work, even though it clearly does not work among American Whites.
VaxGen’s share price dropped by nearly 50% on the day the trial outcome was reported.
A consensus statement developed by several leading AIDS community organisations in the USA, calling for clarification of the AIDSVAX findings, is available online here