Preliminary analysis of data from a clinical trial testing two candidate HIV vaccines given together shows that the combination is safe and can stimulate diverse immune responses against HIV. The findings will be discussed by the study's principal investigator, Robert Belshe, M.D., of Saint Louis University, on Tuesday morning, July 13, at the International Society for Sexually Transmitted Diseases Research meeting in Denver.
This is the second Phase 2 HIV vaccine trial, and the largest to date, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). The trial, known as AVEG 202/HIVNET 014, is being carried out at 14 sites nationwide by two NIAID-sponsored networks, the AIDS Vaccine Evaluation Group (AVEG) and the HIV Prevention Trials Network (HIVNET). Dr. Belshe heads the Saint Louis University AVEG site.
Earlier studies in volunteers at low risk of HIV infection showed this combined vaccine approach held promise for activating both components of the immune system. One vaccine, ALVAC-HIV vCP205, stimulates cellular immunity, resulting in cytotoxic T cells (CTLs) that can kill HIV-infected cells. The other vaccine, SF-2 rgp120, stimulates production of HIV neutralizing antibodies, which can stop HIV from infecting cells. The vaccines contain only selected HIV genes or proteins, and not the whole virus, so an individual cannot become infected from receiving the vaccines.
The current trial, which opened in May 1997, enrolled 435 healthy men and women not infected with HIV. Because the primary goal of this study is to assess the immune response and safety of the vaccine combination in individuals at increased risk of becoming infected with HIV, more than 80 percent of the participants had recent histories of injection drug use or high-risk sexual behavior. All participants received extensive and repeated counseling on reducing high-risk behaviors.
Each participant was randomly assigned to one of three study groups. The first group received both vaccines; the second group received vCP205 and a placebo, or dummy vaccine; and the third group received two placebos. Volunteers received four doses spread out over six months; each time, they got one shot in each arm. By July 1998, all immunizations were completed. The participants will be followed for four years.
Dr. Belshe will report that the vaccines appear safe. Adverse side effects associated with either vaccine were generally mild.
The vaccines have induced anti-HIV immune responses in the majority of the volunteers. More than half of those individuals receiving vCP205 alone, and more than 90 percent of those receiving the vaccine combination, have developed antibodies that can inhibit HIV in a laboratory assay. So far, about one-third of the volunteers receiving either vCP205 alone or the combination vaccine have developed anti-HIV CTL responses. While the results are encouraging and support further evaluation of this vaccine strategy, the study was not designed to determine whether the vaccine combination can protect against HIV infection or AIDS.
Because vaccinated individuals may at times appear positive on a standard HIV antibody test, even though they are not infected, the research team was concerned that participation might put volunteers at risk of discrimination and other negative consequences. True infection, however, can be distinguished from vaccine-induced antibody responses by several tests. Encouragingly, the proportion of volunteers who reported that their participation resulted in a negative event with a major life impact was quite low.
Also reassuring was the fact that overall, participants reported a decrease in risky behaviors after one year in the study. These findings reflected the sustained efforts of the study team to counsel volunteers to practice safe sex and avoid high-risk behaviors.
During the course of the trial, 11 volunteers became infected with HIV as a result of high-risk behaviors: six in the placebo group, three in the group receiving vCP205 alone, and two in the group receiving the vaccine combination. Six of the 11 had received the full four- dose course of vaccine or placebo before becoming infected: three in the placebo group, two in the group receiving vCP205 alone, and one in the group receiving the vaccine combination. However, the trial is neither large enough nor conducted over a long enough period of time to determine vaccine efficacy, says Dr. Belshe.
vCP205, made by Pasteur Merieux Connaught (Lyon, France) with support from the French ANRS (Agence National de Recherches sur le SIDA), consists of a weakened canarypox virus that has been genetically altered to contain a few selected HIV genes. The canarypox virus cannot grow or cause disease in humans. SF-2 rgp120, made by Chiron (Emeryville, CA), is a genetically engineered copy of the HIV surface protein, gp120. SF-2 is a laboratory-adapted HIV strain.
Additional NIAID-sponsored studies are gathering more data on this vaccination strategy before a large-scale efficacy trial is considered. For example, two newer canarypox HIV vaccines are undergoing a head-to-head evaluation. The current study adds compelling new evidence that large-scale efficacy trials using these or similar vaccines are feasible in communities at risk. At this time, the data needed to consider moving into the next phase of testing is expected to be available by late 2000.
For information about AIDS vaccine clinical trials, call the AIDS Clinical Trials Information Service (1-800-TRIALS-A) or visit their Web site at www.actis.org.
NIAID is a component of the National Institutes of Health (NIH). NIAID conducts and supports research to prevent, diagnose and treat illnesses such as HIV disease and other sexually transmitted diseases, tuberculosis, malaria, asthma and allergies. NIH is an agency of the U.S. Department of Health and Human Services.
Press releases, fact sheets and other materials are available on the NIAID Web site at www.niaid.nih.gov.