With the awarding of two five-year contracts, the National Institute of Allergy and Infectious Diseases (NIAID) continues to lay the groundwork for large, multisite trials to examine the effectiveness of promising vaccine candidates that might prevent AIDS in high-risk populations in the United States and abroad.
Abt Associates, Inc. of Cambridge, Mass., will oversee the domestic master contract to conduct feasibility studies and manage multisite HIV vaccine trials in the United States. Family Health International (FHI) of Research Triangle Park, N.C., will administer the international master contract for similar services outside of the United States. Estimated first year costs for the contracts are $4.3 million for Abt and $2.2 million for FHI.
NIAID is committed to providing direction and funding to begin Phase III vaccine efficacy trials as soon as promising candidates are available," says Anthony S. Fauci, M.D., director of NIAID. "While we as yet cannot fully foresee the timing, number, design and magnitude of clinical trials that may be required for testing these candidates, NIAID anticipates that several domestic and international multicenter Phase III efficacy trials could begin between 1994 and 1998."
By the year 2000, up to an estimated 40 million people worldwide--of whom 90 percent are in developing countries--will have been infected with HIV, according to the World Health Organization.
Behavioral changes have reduced the transmission of HIV, but such modifications alone have not stopped HIV from spreading," says Dr. Fauci. "Having a safe, effective vaccine could make a significant impact towards successful, global control of this pandemic."
Preparations to conduct the large efficacy trials of preventive HIV vaccines, including the two master contracts, result from recommendations of an ad hoc committee convened by Dr. Fauci in 1992. The committee suggested that NIAID establish an appropriate infrastructure to assure that sites would be ready to begin such trials when suitable candidate vaccines were identified.
In response, the institute developed plans for the HIV Vaccine Efficacy Trials Network (HIVNET), including the master contracts, which received approval from the NIAID AIDS Research Advisory Committee, a congressionally mandated panel of representatives from advocacy groups, federal agencies, industry, the scientific community and physicians who care for people with HIV.
In addition, HIVNET will include a statistical and data coordinating center, a laboratory and a specimen repository that will manage data, conduct specialized testing and store blood samples from the trials conducted under the master contracts. Rodney Hoff, Sc.D., chief of the Vaccine Trial Section in the Vaccine and Epidemiology Branch of NIAID's Division of AIDS, is the project officer for both master contracts. Biomedical Research, Inc. of Rockville, Md., holds the repository contract. Contracts for the center and the laboratory are expected to be awarded by the end of 1993 and the beginning of 1994, respectively.
Already in the United States, NIAID has completed 3 trials and is conducting 12 trials of several HIV vaccine candidates at the institute's AIDS Vaccine Evaluation Units (AVEUs). Specifically, investigators of these phase I and II studies are evaluating the vaccines' safety and ability to stimulate the immune system in more than 1,250 men and women uninfected with HIV. The five AVEUs are at Johns Hopkins University in Baltimore, Md., St. Louis University, Mo., University of Rochester, N.Y., University of Washington in Seattle and Vanderbilt University in Nashville, Tenn.
In late 1992, NIAID launched the first Phase II trial of a preventive HIV vaccine in the AVEUs. Unlike the earlier trials, some participants in this study have a history of behavior that puts them at high risk for HIV infection--injection drug use, multiple sex partners or a sexually transmitted disease. As part of the trial, they receive repeated counseling to avoid such high-risk behavior. In addition to providing safety and immunogenicity data, the trial will help determine if such individuals, representative of people likely to enroll in large-scale trials, respond differently to vaccines.
Under both master contracts, Abt and FHI will assess the number of HIV-infected people and the feasibility of recruiting and retaining 500 to 1,000 uninfected people at potential sites for large phase III trials. In the international setting, FHI will conduct small phase I/II trials to see if results agree with those found in the AVEU studies in the United States. Pilot studies will precede the large trials. Then Abt and FHI will conduct the large trials to compare the vaccine candidates to a placebo, and neither the participants nor the investigators will know which product an individual received until the trial ends. The organizations also may test other biomedical interventions to prevent HIV infection.
NIAID is one of the 17 institutes of the National Institutes of Health, an agency of the U.S. Department of Health and Human Services and the federal focal point for health research. NIAID's expert scientists study AIDS and HIV disease, tuberculosis, allergies, asthma, Lyme disease, transplantation and basic immunology with an emphasis on prevention, diagnosis and improved treatment.
In addition to its laboratories in Bethesda, Md., and Hamilton, Mont., NIAID supports research and training of nonfederal scientists at universities, medical schools, hospitals and research institutions throughout the United States and abroad.