AIDSVAX Trial Results Stir ‘Controversy’ Over Small Population Subset Showing Protection in Blacks, Asians

Brisbane, Calif.-based biotech firm VaxGen's announcement yesterday that its experimental AIDS vaccine AIDSVAX appeared to be effective among African Americans, Asians and other non-white, non-Hispanic volunteers -- but largely ineffective among the rest of the study's participants -- has stirred "controversy" in the "pent-up world of AIDS vaccine research," USA Today reports (Sternberg, USA Today, 2/25). The company said that the vaccine reduced the rate of new HIV infections by only 3.8% among people who received the vaccine, compared with clinical trial participants who received placebo injections. The study consisted of 5,108 gay or bisexual men and 309 women who were at high risk for HIV infection because they had sex partners who injected drugs or had sex with men, and all of the participants received constant counseling on how to prevent HIV infection and were told not to rely on the vaccine to protect them from infection. All of the participants were HIV-negative when they began the study. About twice as many people were randomly assigned to receive injections of the vaccine than were assigned to the placebo group, and participants were recruited to trial locations in the United States, Canada, Puerto Rico and the Netherlands. The vaccination schedule included three shots every three months, followed by booster shots every six months. The analyzed data only included the 5,009 participants who received at least three shots (Kaiser Daily HIV/AIDS Report, 2/24). VaxGen said that four of the 203 black volunteers who received the vaccine tested HIV-positive, compared to nine of 111 who received the placebo, the Philadelphia Inquirer reports. Of 53 Asians who received the vaccine, two tested positive for HIV, compared to two of 20 in the placebo group. VaxGen said those results were "statistically significant" and demonstrated that the vaccine "had value." But others say the size of the subgroups is "too small" to draw conclusions, the Inquirer reports (Flam, Philadelphia Inquirer, 2/25).

Size Matters
Some HIV/AIDS advocates yesterday claimed that VaxGen was "obsfucati[ng]" the results of the study, the Wall Street Journal reports. Gregg Gonsalves, director of treatment and prevention advocacy at Gay Men's Health Crisis, said, "My sense is that they're way out in front of the data" (Hamilton, Wall Street Journal, 2/25). National Institute of Allergy and Infectious Disease Director Dr. Anthony Fauci agreed that any "possible benefit" of the vaccine was based on preliminary statistical analyses, the New York Times reports. He said that his agency would carry out a series of laboratory tests on blood samples from the trial to "uncover any possible immune or genetic factor" that could explain the results. Fauci said that his agency would test for antigen indicators of whether a person is "more susceptible to infections or less likely to respond to certain vaccines," according to the Times. He also said that they would examine how the cells respond to exposure to certain components of the virus. Fauci added that the results were "provocative enough to give very good reason to consider funding a larger study of this or other AIDS vaccines among minorities" (Altman, New York Times, 2/25). However, Dr. John Moore of the New York Weill Cornell Medical Center said that the racial data are "a statistical artifact" based on the small subgroup of minorities. He added that there is "no biological reason based on how the vaccine works that race would make a difference." Moore said that VaxGen "played the race card ... because (the company) had to show some results to its public investors" (Maugh/Gellene, Los Angeles Times, 2/25).

Continuing Efforts
VaxGen said that "despite disappointing results" from the trial, the company will continue its efforts to gain FDA approval for the vaccine, the Washington Post reports. VaxGen President and Co-Founder Donald Francis said, "The question is whether we [move toward licensure] with this study or other ones" (Brown et al., Washington Post, 2/25). The FDA has already fast-tracked the review process for AIDSVAX (Kaiser Daily HIV/AIDS Report, 2/24). Even though it is "too early to say" if the agency will ask VaxGen to perform further trials involving African Americans and other minorities, the company is attempting to "build support for the vaccine," the San Francisco Chronicle reports. VaxGen CEO Lance Gordon said, "If we announced to the world that we were abandoning the project because the study failed in whites, we'd be crucified." Gordon this week is set to present the findings to the CDC's Advisory Committee on Immunization Projects, and he will also present the results to the African American AIDS Policy and Training Institute (Abate, San Francisco Chronicle, 2/25). VaxGen later this year is expected to announce the results of another trial of a similar version of the vaccine that included 2,400 injection drug users in Thailand (Kaiser Daily HIV/AIDS Report, 2/24).

VaxGen Stock Falls
Following the company's announcement yesterday, VaxGen's shares "lost nearly half their value," dropping from $13.02 to $6.86 per share, the New York Times reports. Analysts said the trial results indicate that the company has "virtually zero percent chance" of having the vaccine approved for use in early 2005 as it had planned. Jon Alsenas of ING Management said, "If one or two people had gone in the opposite direction [in the vaccine trial], just one or two, they would have lost statistical significance. Would you invest ... on one or two people going in a different direction?" (Pollack, New York Times, 2/25). Francis, when asked if the results "warranted" further investment, said, "We've proved that humans can be protected from HIV, even if it's four people. ... If society values this damn stuff, they better move it forward" (Gellene, Los Angeles Times, 2/25). Ron Garren, chief biotechnology strategist at InvestBio, said that the vaccine's "bleak prospects" for FDA approval do not mean that the vaccine is "dead," according to the Times. He added that the "natural market" for the vaccine -- especially if it proves effective in minorities -- would be in Africa and Asia, where the epidemic is widespread (New York Times, 2/25).

Reaction
Many AIDS advocacy groups responded yesterday to the AIDSVAX trial results. Some of their responses appear below, listed in alphabetical order:

• AIDS Healthcare Foundation: Stating that the results showing a possibility of protection among blacks and Asians is "perhaps encouraging," AHF President Michael Weinstein said that the results "require that we reassess our strategy of vaccine development." He added, "Clearly work should continue where the trial showed promise, but the general results suggest that 20 years into this pandemic we really need to stop and take a long hard look at this issue." AHF Chief of Medicine Charles Farthing said, "To me, it looks now very unlikely we will ever have a protective vaccine against HIV," adding, "I now feel strongly that more resources should be put into providing antiretroviral therapy -- which we know works and works well -- for people in resource-poor settings than into vaccine research" (AHF release, 2/24).
  
• AIDS Project Los Angeles: David Pieribone, APLA associate director of education, said that the results give "a number of reasons to be optimistic." He continued, "First, the study was a success in that it showed that high participant retention rates are possible. Secondly, researchers noted that study participants did not increase their risky behavior even if they thought they had been vaccinated. Finally, further analysis of the data may provide a better understanding of the type of immune response needed to protect against HIV infection, which will surely help improve future attempts to design an effective HIV vaccine" (APLA release, 2/24).
  
• AIDS Vaccine Advocacy Coalition, Project Inform, Treatment Action Group: The three organizations yesterday released a consensus statement, saying, "We fear that VaxGen has deliberately emphasized these putatively positive findings, ... while failing to emphasize that they are based on very small numbers of infections in a limited sample of participants. This may serve the commercial interests of the company, but it does a great and profound disservice to the HIV-affected communities who must now struggle to make sense of the press stories that the VaxGen release has generated" (AVAC/Project Inform/TAG release, 2/24).
  
• Gay Men's Health Crisis: GMHC expressed its "strong suppor[t]" of AIDS vaccine research, including VaxGen's efforts, but criticized the company for promoting trial results that are based on subgroup data. "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," Gonsalves said (GMHC release, 2/24).
  
• Global Health Council: Nils Daulaire, president and CEO of the Global Health Council, said, "While these results are 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." Daulaire added, "We should redouble our efforts at finding an AIDS vaccine and assure funding to pursue all promising avenues. ... In the meantime, expanded efforts to educate, treat and prevent must carry the load of our global fight against this killer (Global Health Council release, 2/24).
  
• Project Inform: "The company is claiming that this vaccine works better in African Americans and other non-Hispanic racial subgroups based on a difference of five people," Project Inform's Founding Director Martin Delaney said, adding, "This is at best premature and irresponsible data reporting. It is highly misleading and disingenuous to communities who have a stake in these findings. It would do a great deal of harm to stir up hopes for selected groups over a vaccine that has been proven ineffective overall" (Project Inform release, 2/24).
  
• San Francisco AIDS Foundation: SFAF Executive Director Pat Christen commended VaxGen "for proving that successful enrollment and retention of trial participants is possible," adding, "It is a remarkable and historic accomplishment" (SFAF release, 2/24).
  
• WHO/UNAIDS: Stating that HIV vaccine research "remains an urgent global need," World Health Organization Director-General Gro Harlem Brundtland said, "We will need many more trials to develop effective HIV vaccines, particularly against the most prevalent HIV sub-types which are having a devastating impact on populations in sub-Saharan Africa." UNAIDS Executive Director Peter Piot said, "These results are promising. The trial provides clear evidence that a vaccine can work." Piot added, "However, there is an urgent need for more targeted research to find out why the candidate vaccine only seems to work in certain population subgroups. In the meantime, we must continue to expand existing prevention efforts, which have proved their effectiveness when they are implemented at full scale" (WHO/UNAIDS release, 2/24).
  

Media Coverage
The following broadcast programs reported on VaxGen's AIDSVAX trial results announcement:

• ABC's "World News Tonight": The segment includes comments from Dr. Seth Berkley from the International AIDS Vaccine Initiative and Moore of the New York Weill Cornell Medical Center (Potter, "World News Tonight," ABC, 2/24). The full segment is available in RealPlayer online.
  
• CBS' "Evening News": The segment includes comments from VaxGen Vice President Phillip Berman, AVAC Executive Director Chris Collins, Francis, Gonsalves, Piot and vaccine study volunteer Tom Shroeder (Kaledin, "CBS Evening News," CBS, 2/24). A transcript and video of the segment in RealPlayer are available online.
  
• CNN's "American Morning with Paula Zahn": Zahn discusses the results with CNN medical correspondent Sanjay Gupta (Zahn, "American Morning with Paula Zahn," CNN, 2/24). The transcript of the segment is available online.
  
• CNN's "Live at Daybreak": CNN correspondent Fredricka Whitfield discusses the findings with Gupta (Whitfield, "Live at Daybreak," CNN, 2/24). The transcript of the segment is available online.
  
• NBC's "Nightly News": The segment includes comments from Berman, Fauci and Moore (Bazell, "Nightly News," NBC, 2/24). A transcript and video of the segment in Windows Media format are available online.
  
• NPR's "All Things Considered": The segment includes comments from Berkley, Francis and Brown University researcher Dr. Kenneth Mayer, who helped conduct the vaccine study (Harris, "All Things Considered," NPR, 2/24). The full segment is available in RealPlayer online.
  
• NPR's "All Things Considered": Host Robert Siegel interviewed Dr. David Baltimore, former chair of the NIH AIDS Vaccine Research Working Group and current president of the California Institute of Technology (Siegel, "All Things Considered," NPR, 2/24). The full segment is available in RealPlayer online.
  
• NPR's "All Things Considered": Commentator Joe Wright, a former community educator for a government-sponsored HIV vaccine trial network, says the study's finding that the vaccine might work in some minorities is a reminder that diversity is important for clinical trial recruitment (Wright, "All Things Considered," NPR, 2/24). The full segment will be available in RealPlayer online.
  
• PBS' "NewsHour with Jim Lehrer": A transcript of the news summary provided at the beginning of last night's show is available online ("NewsHour with Jim Lehrer," PBS, 2/24).