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 2,100 healthy, non-HIV-infected adult volunteers have enrolled in 27 NIAID-supported trials involving 17 vaccines. Approximately 80 percent of these individuals have received vaccines, and the remainder (20 percent) have received placebos. The trials have been conducted at university-based AIDS Vaccine Evaluation Group (AVEG) sites throughout the United States. NIAID investigators have carried out an additional trial involving 120 volunteers at the National Institutes of Health Clinical Center in Bethesda, Md., and currently are enrolling volunteers in a new trial of a DNA vaccine.
The 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 from the vaccines.
Participants have tolerated the vaccines well, and investigators have identified no pattern of unexpected or significant adverse events related to immunization. To date, 26 participants have become infected with HIV in the course of the AVEG studies. Of the 26, four were among those who received placebo and 22 were among those who received vaccines. In addition, three participants who received vaccines in NIAID's intramural trial became infected. The proportion of volunteers who have become infected is similar in both the placebo and vaccination groups.
While it is clear that these vaccines are less than 100 percent effective in preventing HIV infection, no further conclusions regarding their effectiveness can be drawn. Some participants became infected before a full course of planned immunizations. In addition, because the size of the trials and numbers of infections are too small, the overall efficacy of the vaccines in preventing either infection or disease cannot be evaluated.
Investigators expect that some individuals in HIV vaccine trials will become infected despite careful counseling about ways to reduce their risk of HIV infection. All infections among the trial participants are the result of high-risk behaviors such as unprotected sex with an HIV-infected individual or injection drug use. At present, none of the HIV-infected participants has symptoms of AIDS, although two vaccinated individuals who became infected with HIV 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 some HIV-infected people who had not participated in vaccine trials.
The 29 volunteers who became infected after engaging in high-risk behaviors were enrolled in the following trials:
--> one in AVEG 010, testing gp160 vaccines made by Bristol-Myers Squibb/Oncogen and IMMUNO-AG, and gp120 vaccines made by Genentech and Biocine; --> one in AVEG 015, testing a gp120 vaccine manufactured by Biocine; --> three in AVEG 016, testing a gp120 vaccine manufactured by Genentech; --> 15 in AVEG 201, testing two gp120 vaccines, one manufactured by Genentech and one by Biocine; --> two in AVEG 002, testing gp160 vaccines made by Bristol-Myers Squibb/Oncogen and MicroGeneSys; --> two in AVEG 003 trial, testing a gp160 vaccine from MicroGeneSys; --> one in AVEG 007, testing a gp120 vaccine manufactured by Biocine; --> one in AVEG 013, testing a gp160 vaccine made by IMMUNO-AG; --> three in an NIAID intramural trial, testing the gp160 vaccine from MicroGeneSys.
The Bristol-Myers Squibb/Oncogen vaccine is a recombinant vaccinia virus producing a copy of the HIV envelope protein. All of the other vaccines are purified copies of the HIV envelope protein.
Prior to enrollment, potential volunteers are educated regarding HIV and its modes of transmission, extensively counseled regarding possible exposure to the virus, and warned that the protective effects of the candidate vaccines against HIV infection are unknown. Volunteers also are told if the vaccine trial includes placebos. Once enrolled, participants 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, in people who receive a vaccine, the course of HIV disease might be the same, slower or faster, on average, than in non-vaccinated, HIV-infected people.
To ensure that study participants are fully informed of all potential risks in these early trials, the informed consent documents used in NIAID HIV vaccine trials clarify and emphasize the possible risks to vaccinated individuals.
The National Institute of Allergy and Infectious Diseases, a component of the National Institutes of Health (NIH), supports research on AIDS, tuberculosis and other infectious diseases, as well as allergies and immunology. NIH is an agency of the U.S. Department of Health and Human Services.
Prepared by: Office of Communications National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda, MD 20892 U.S. Department of Health and Human Services