Important note: Information in this article was accurate in December 2000. The state of the art may have changed since the publication date. HIV vaccine advocates, like other interest groups, witnessed the US Presidential inauguration in January 2001 without a clear sense of where the new president may be headed. Following a truncated transition and a campaign in which AIDS issues did not figure prominently, observers were left to discern hints from the political tea leaves.
Reports indicate that Secretary of State Colin Powell has shown particular interest in the impact of AIDS in Africa, while it seems likely that the Bush administration might adopt the enthusiasm of Congressional Republicans for long-term increases in biomedical research spending. Tommy Thompson, the new Secretary of Health and Human Services, supported energetic HIV care initiatives in his home state of Wisconsin, although he was reportedly less supportive of spending for behavioral prevention interventions.
Despite these early signs, important questions remain. The administration is reviewing former President Clinton's executive order that prohibited US government intervention to prevent developing countries from using compulsory licensing or parallel importation to expand access to HIV drugs. Further, the President's ban on U.S. funding to overseas family planning organizations that offer abortion counselling could hinder their AIDS prevention efforts. It is also unclear how much emphasis will be placed on foreign aid, especially the sort not tied to traditional geopolitical notions of American self-interest. According to Washington insiders, the details of the Presidents first budget may not emerge before April.
The search for a new director of the Office of AIDS Research at the US National Institutes of Health (NIH) is underway, with a search committee now reviewing candidates. The post became vacant when Neal Nathanson retired in September 2000. Observers say it could be difficult to replace the well-respected Nathanson who, in the opinion of many, combined a sterling academic reputation with a pragmatic approach to moving research forward. Nathanson, a strong advocate for AIDS vaccine research, is returning to a professorship at the University of Pennsylvania. He also serves on NIHs AIDS Vaccine Advisory Committee and IAVI's Scientific Advisory Committee.
On 28 November 2000, Australian regulatory authorities approved a Phase I/II therapeutic vaccine trial of a recombinant fowlpox vector (rFPV) containing the HIV gag and pol genes. The study will compare rFPV alone to rFPV co-expressing the human cytokine interferon (IFN)-gamma and to placebo, examining both the safety of these regimes and their ability to enhance HIV-specific killer T-cells during the early stages of infection. The trial will enroll 36 recent seroconverters on anti-retroviral therapy.
The vaccine was developed by Ian Ramshaw (Australian National University, Canberra), David Boyle (CSIRO, Geelong) and Stephen Kent (University of Melbourne) and is licensed to Virax Holdings in Melbourne, which is funding the study. The trial will be conducted at three sites under the auspices of the National Centre in HIV Epidemiology and Clinical Research at the University of New South Wales and is expected to start in February or March 2001.
The same constructs will also be used as part of a preventive vaccine being developed with NIH funding. That strategy uses a DNA prime + rFRV boost approach, with or without co-expression of either IFN-gamma or IL-12 in the boost.
Plans for a 10,000 person efficacy study of Remune®, a whole-killed HIV therapeutic vaccine developed by the late Jonas Salk, are on hold following questions over interpretation of earlier trial data and concerns of financial conflict of interest for its principal investigator. Permission to conduct the trial was sought from Thai authorities by Vina Churdboonchart on behalf of the Trinity Medical Group (TMG), which licensed commercial rights to Remune® (from the California-based Immune Response Corporation) in several Asian countries.
Trouble began when the subcommittee questioned differences between Churdboonchart's analysis of a 300-person study of Remune® given without anti-HIV drugs to HIV-infected Thai volunteers. While she claims that increases in CD4 counts among Remune® recipients are statistically significant, Harvard statistician Steve Lagakos sees only a trend in this direction.
Another controversial study comparing HAART plus Remune® to HAART alone reported no additional benefit of Remune® (JAMA 2000 Nov 1;284(17):2193-202). Yet some scientists have criticized the study design. Bruce Walker of Massachusetts General Hospital said the study "does little to resolve issues related to effectiveness of Remune® [since] the endpoints called it a failure if there were any minor increases in viral load in those receiving the vaccine." In his own recent treatment interruption trial – which succeeded in getting "a significant fraction" of volunteers off therapy thus far, viral load initially increased before the immune system kicked in. "All of these subjects would have been considered failures by the criteria of the JAMA paper," said Walker. Although skeptical of using therapeutic vaccines without concurrent anti-viral treatment, he warned that therapeutic vaccines should not be evaluated by the same criteria as HAART, as this could lead to "prematurely dismissing an agent that may ultimately be of some benefit."
That leaves the Thai trial still hanging. With the conflict-of-interest issue apparently resolved, Thailand's subcommittee on vaccine evaluation will revisit the scientific questions at its next meeting.
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©2000. The IAVI Report.
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