HIV VACCINE TRIALS COULD USE INFECTION AS ENDPOINT

Executive Summary

HIV VACCINE TRIALS COULD USE INFECTION AS ENDPOINT rather than prevention of clinical disease, an expert panel established by the White House Office of Science and Technology concluded in a report on HIV vaccine development and international trials released Nov. 3. While acknowledging that the prevention of AIDS is the optimal endpoint of an HIV vaccine, the report states that the HIV/AIDS epidemic justifies an "alternative strategy." "Given the urgency of the epidemic, time does not permit following the population for a decade or more," the report notes. "Although prevention of persistent infection may not be necessary to prevent disease, it is by far the preferred outcome," the report states. Infection prevention or limitation of progression could be ascertained by several virologic markers in the blood, the report suggested. These include: "virus genes, as measured by polymerase chain reaction; virus antigens, as measured by immunoassay; viremia, as measured by isolation and cultivation of virus; or antiviral antibodies to antigens not present in the vaccine formulation, as measured by immunoassay or immunoblot." Speculating on possible outcomes of an HIV vaccine efficacy trial with infection as an efficacy endpoint, the report notes that an "HIV vaccine may show strong short-term virologic evidence of efficacy, such as apparent complete prevention of infection for two years or longer." With that type of data, the report recommends, "preliminary licensure should be considered." The report asserts that "long-term clinical efficacy may be assumed, but must be verified by continued follow-up of recipients." OSTP's 30-member panel, the Working Group on HIV Vaccine Development and International Field Trials, is convened under the aegis of the Federal Coordinating Council for Science, Engineering and Technology (FCCSET). The group is chaired by Walter Dowdle, PhD, Centers for Disease Control and Prevention, and is co-chaired by National Institute of Allergy & Infectious Diseases Director Anthony Fauci, MD, and Col. Donald Burke, MD, of the Walter Reed Institute of Research. The only FDA representative on the panel was former Center for Biologics Evaluation & Research Office of Blood Research and Review Director Gerald Quinnan, MD. He recently left the agency. The report is the first issued since the group's initial meeting in April 1992. The group is charged with assessing problems related to the development and testing of HIV vaccines and must report to the chair of FCCSET's committee on life sciences and health at least annually. The document addresses ethical, scientific, political and logistical concerns surrounding HIV vaccine development and trials. In the preface, OSTP Director John Gibbons states that the document will be distributed to Congress, as well as to national and international research communities and health policy agencies, to facilitate development of a "successful worldwide campaign against AIDS." The report also recommends the establishment of "review committees" that represent the views of the community where an HIV vaccine trial is being conducted to protect participants in the trial. Additionally, prior to the start of a trial, the report advises that "independent data and safety monitoring boards to monitor the conduct of trials must be rigorously defined and set up." These boards, the report continues, "will have the authority to recommend stopping trials if they are unsafe, if they have achieved a definitive result, or if they cannot reach a definitive result." Furthermore, the report notes that "before the start of international field trial, agreement should be reached among U.S. investigators, vaccine manufactures, and host governments about realistic approaches toward making effective vaccines available to the country."