The National Institute of Allergy and Infectious Diseases (NIAID) supports studies of experimental vaccines intended to prevent infection and disease caused by the human immunodeficiency virus (HIV). Since 1988, More than 1,400 healthy, non-HIV infected adult volunteers have enrolled in 17 NIAID-supported trials involving 12 vaccines. Approximately 83 percent of these individuals have received vaccine and the remainder received placebo. The trials have been conducted in the U.S. at five university-based AIDS Vaccine Evaluation Group (AVEG) sites. NIAID investigators have carried out additional trials at the National Institutes of Health in Bethesda, Md.
The initial trials conducted to date have tested the safety and the effects on the immune system of several candidate vaccines made by genetic engineering techniques or by chemical synthesis. Because the vaccines do not contain infectious or altered virus, volunteers cannot become infected with HIV as a result of vaccination.
Participants have tolerated the vaccines well, and investigators have not identified any pattern of unexpected or significant adverse events related to immunization. In the course of the AVEG studies seven adult participants have become infected with HIV. Of the seven, two were among the 17 percent who received placebo and five were among the 83 percent who received vaccine. An additional three participants who received vaccines in NIAID's intramural trials have become infected.
It was expected that some individuals, in spite of careful counselling, would become infected, and all infections appear to be the result of high-risk behaviors such as injection-drug use or unprotected sex with an HIV-infected individual. At present, none of the HIV-infected participants has symptoms of AIDS, although one vaccinated individual who became infected with HIV has experienced a rapid loss of CD4+ T cells. Investigators do not know whether this rapid CD4+ T cell decline is related to vaccination; similar rates of CD4+ T cell loss have occurred in HIV-infected people who are not participating in vaccine trials.
Of those who became infected with HIV after entering an NIAID-supported trial, one participant was enrolled in the AVEG 016 trial of a gp120 vaccine manufactured by Genentech; three were enrolled in the AVEG 201 trial of two gp120 vaccines, one manufactured by Genentech and one by Chiron/Biocine; one was enrolled in the AVEG 002 trial of gp160 vaccines made by Bristol-Myers Squibb/Oncogen and MicroGeneSys; and two were enrolled in the AVEG 003 trial of a gp160 vaccine from MicroGeneSys, although these two participants had received placebo. Three participants had received a gp160 vaccine from MicroGeneSys in NIAID intramural trials. Prior to enrollment, potential volunteers are educated regarding HIV and its modes of transmission, extensively counselled regarding possible exposure to the virus, and warned that the protective effect of the candidate vaccines against HIV infection is unknown. Volunteers also are told if the vaccine trial includes placebos. Once enrolled as participants, people are cautioned that they must not expect the experimental vaccine to protect them against HIV infection or AIDS. They are informed that a vaccinated person might be less or more likely to become infected by HIV if exposed to the virus. Investigators also tell participants that no one knows what effect the vaccine might have on a person who does become infected with HIV. For example, the course of HIV disease in people who receive a vaccine might be the same, slower or faster than non-vaccinated, HIV-infected people, on average.
In light of the rapid loss of CD4+ T cells in one vaccine recipient who has become HIV positive, and to ensure that study participants are fully informed of all potential risks in these early trials, investigators are modifying the informed consent documents used in the NIAID HIV vaccine trials to further clarify and emphasize the possible risks to vaccinated individuals. The institutional review boards at participating institutions will examine the revised consent forms along with the information on which these modifications are based.
Many concerns, in addition to safety, will affect whether NIAID will choose to go forward with larger trials of any of these candidate vaccines. Laboratory, animal model and clinical trial results were discussed at length by the NIAID's Vaccine Working Group, which met in April 1994, to consider all of the information currently available about the safety and potential efficacy of the vaccines. On June 17, 1994, the NIAID's AIDS Research Advisory Committee will discuss these and other issues, including trial designs, feasibility considerations, and concerns of volunteer communities, before presenting recommendations to the NIAID Director.
The National Institute of Allergy and Infectious Diseases, a component of the National Institutes of Health, supports research on AIDS, tuberculosis and other infectious diseases as well as allergies and immunology. NIH is an agency of the U.S. Public Health Service, U.S. Department of Health and Human Services.Prepared by: