HIV Prevention Efficacy TrialsDate: May 1, 1997
Source: National Institutes of Health (NIH)
Author: National Institute of Allergy and Infectious Diseases (NIAID)
The National Institute of Allergy and Infectious Diseases (NIAID) is committed to developing and testing experimental vaccines and other interventions to prevent the transmission of HIV infection and disease progression.
To this end, NIAID established the HIV Network for Prevention Trials (HIVNET) in 1993 to conduct efficacy trials of promising HIV prevention strategies in both the United States and abroad. HIVNET is a cooperative group of investigators who primarily evaluate the safety and efficacy of interventions to prevent the sexual, perinatal and parenteral transmission of HIV. HIVNET's main area of emphasis is vaccines but it also encompasses other interventions: topical microbicides, sexually transmitted disease (STD) treatment, prophylaxis to prevent mother-to-infant transmission and behavioral risk reduction strategies. To accomplish its main mission, HIVNET supports randomized, controlled clinical trials that use HIV seroincidence as the primary endpoint. HIVNET also conducts a range of other studies, such as baseline seroincidence surveys, that lead to or support prevention efficacy trials.
HIVNET has five parts:
--> A domestic master contractor, awarded in October 1993 to ABT Associates of Cambridge, Mass. In September 1994, ABT awarded subcontracts to eight field sites to evaluate candidate interventions in U.S. populations.
--> An international master contractor, awarded in October 1993 to Family Health International (FHI) of Research Triangle Park, N.C. In September 1994, FHI subcontracted with nine field sites to conduct trials in populations outside the United States.
--> A statistical and data coordinating center provides statistical and data management support for the domestic and international trials. NIAID awarded this contract in March 1994 jointly to the Fred Hutchinson Cancer Research Center and the University of Washington.
--> A central laboratory contractor provides laboratory support for specialized testing of populations in the domestic and international trials. NIAID awarded this contract in March 1994 to Public Health Enterprises of Los Angeles, Calif., with the California State Health Laboratory in Berkeley as a subcontractor.
--> A specimen repository serves the domestic and international trials. NIAID renewed this contract with Biomedical Research, Inc., of Rockville, Md., in June 1994.
HIVNET studies often engage collaborators at other institutes within the National Institutes of Health and at the Centers for Disease Control and Prevention, the U.S. Army, and various national and international health organizations.
To foster trust and mutual understanding of clinical trialissues, and to ensure that the studies respect cultural and ethnic differences among participants, HIVNET has involvedcommunity members in all phases of the research process.
Highlights of HIVNET Accomplishments and Future Plans
Vaccine Preparedness Study
The eight domestic HIVNET sites have undertaken a multicenter Vaccine Preparedness Study (VPS), to be completed in April 1997, to determine the feasibility of conducting an HIV vaccine efficacy trial. Close to 4,900 participants at high risk for HIV infection (gay men, injection drug users and women at risk through heterosexual contact) are enrolled in the VPS, which simulates the size of a large-scale vaccine trial. Overall, HIV seroincidence in this cohort has been stable at 2 percent per year, with a 95 percent retention rate after one year of follow-up. Willingness to participate in vaccine trials has been high and is being monitored in response to new information about trials and vaccine products.
International Cohort Study
HIVNET currently sponsors international projects in nine countries: five in Africa, two in Asia and two in the Americas. The sites have recruited and followed more than 12,000 people at high risk for HIV infection (female commercial sex workers, gay men, STD clinic patients, truck drivers, factory workers and pregnant women). The annual HIV seroincidence at these sites ranges from less than 1 percent to greater than 12 percent, with one-year follow-up rates ranging from 70 to 94 percent. HIV strains isolated from participants in the diverse cohorts represent all the major HIV subtypes.
One promising vaccine concept, the ALVAC vcp205/gp120 combination, will soon be ready for expanded testing, and HIVNET will be evaluating this concept over the next few years. A series of trials of this vaccine candidate are in various stages of planning. A Phase II trial in the United States to assess the safety and immunogenicity of the ALVAC vcp205/gp120 combination which HIVNET will conduct in collaboration with the AIDS Vaccine Evaluation Group is now under way.
In addition to U.S. studies, HIVNET has designed a Phase I study to assess the safety and immunogenicity of the ALVAC vcp205 vaccine alone in African populations, scheduled to begin in the Spring of 1997 at the Uganda site. Data from this study will be used to develop an appropriate ALVAC HIV vaccine for East African countries.
HIVNET also is providing supplemental support for a community advisory board for an ongoing HIV gp120 vaccine trial in Thailand, sponsored by the Walter Reed Army Institute of Research.
An efficacy study in the Malawi site, which was jointly funded by the National Cancer Institute, evaluated the effect of chlorohexidine wash of the birth canal to prevent perinatal transmission of HIV. Although chlorohexidine had no effect on virus transmission, it produced a significant drop in the rate of neonatal sepsis. Another Phase III study is planned to begin at the proposed Dominican Republic site in June 1997 to examine the effect of HIV immunoglobulin on preventing perinatal transmission.
In November 1996, the Uganda site began a Phase I study of the safety of nevirapine in seropositive pregnant women and their newborns. If the study demonstrates no safety concerns, HIVNET will proceed with a Phase II/III trial in Uganda to evaluate peripartum use of nevirapine or zidovudine (AZT) compared with placebo in preventing perinatal transmission. HIVNET also will consider evaluating other promising antiretroviral drugs (e.g., PMPA, protease inhibitors) as soon as initial safety studies are completed in the United States.
After successfully completing a Phase II safety study of a nonoxynol-9 (N-9) vaginal microbicide gel in January 1996, the Kenya site began a Phase III efficacy trial of this product in July 1996 to determine if it can prevent sexual transmission of HIV among commercial sex workers.
To further clinical development of novel topical microbicide products for vaginal use, HIVNET has planned a series of Phase I/II trials to establish the safety and acceptability of new products in different populations. In December 1996, the Boston site began a study in Rhode Island examining the safety and acceptability of an acid buffer gel. If no safety concerns arise in U.S. participants, the trial will be extended to HIVNET sites in Thailand, India, Malawi and Zimbabwe.
Microbicide products such as N-9 have been used rectally, but it is not known if these products are safe or effective when used in this manner. Therefore, HIVNET is conducting a Phase I safety study of an N-9-containing gel for rectal use. HIVNET researchers also are searching for more acceptable and effective delivery systems for these products.
The Zimbabwe site is currently conducting a randomized community trial of peer counseling to prevent sexual transmission of HIV in factory workers. The sites in Thailand, India and Uganda are developing a joint Phase I study of condom promotion to prevent heterosexual HIV transmission among stable couples in which one partner is infected and the other is not.
The domestic sites also are planning a trial to evaluate individualized behavioral counseling as a way to reduce HIV and/or STD transmission in gay men.
Domestic HIVNET Field Sites:
Denver Department of Public Health, Denver, CO Principal Investigator: Frank Judson, M.D.
Fenway Community Health Center, Boston, MA Principal Investigator: Kenneth Mayer, M.D.
Howard Brown Health Center, Chicago, IL Principal Investigator: David McKirnan, Ph.D.
New York Blood Center, New York, NY Principal Investigator: Cladd E. Stevens, M.D. Co-Principal Investigator: Beryl A. Kobin, Ph.D.
New York University, New York, NY Principal Investigator: Michael Marmor, Ph.D.
San Francisco AIDS Office/Public Health Foundation Enterprises, Inc., San Francisco, CA Principal Investigator: Susan Buchbinder, M.D.
University of Pennsylvania, Philadelphia, PA Co-Principal Investigators: George Woody, M.D. David Metzger, Ph.D.
University of Washington, Seattle, WA Principal Investigator: Connie Celum, M.D.
International HIVNET Field Sites:
Case Western Reserve University/Makerere University, Kampala, Uganda Principal Investigator: Jerrold Ellner, M.D. Co-Investigator: Roy Mugerwa, M.B.Ch.B., M.Med.
Harvard University/Universite Cheikh Anta Diop, Dakar, Senegal Principal Investigator: Phyllis Kanki, M.D. Co-Investigator: Souleymane Mboup, M.D.
Johns Hopkins University/Centers for Development and Health, Chaing Mai, Thailand Principal Investigator: Kenrad Nelson, M.D. Co-Investigators: Chirasak Khamboonruang, M.D. Chawalit Natpratan, M.D.
Johns Hopkins University/Program for the Control of STDs and AIDS, Santo Domingo, Dominican Republic (proposed site) Principal Investigator: Neal A. Halsey, M.D. Co-Investigator: Ernesto Guerrero, M.D., M.P.H.
University of Pittsburgh/Federal University of Rio De Janeiro, Brazil Principal Investigator: Lee H. Harrison, M.D. Co-Investigator: Mauro Schecter, M.D., Ph.D.
Johns Hopkins University/Malawi College of Medicine, Blantre, Malawi Principal Investigator: Taha E.T. Taha, M.D. Co-Investigators: George Liomba, M.D. Newton Kumwenda, Ph.D. Robert Broadhead, M.D.
Johns Hopkins University/National AIDS Research Institute (NARI), Pune, India Principal Investigator: Robert C. Bollinger, M.D., M.P.H. Co-Investigators: Sanjay Mehendale, M.D., M.P.H. Deepak A. Gadkari, M.D.
Stanford University/Zimbabwe AIDS Prevention Project (ZAPP), Harare, Zimbabwe Principal Investigator: Julie Parsonnet, M.D. Co-Investigators: Ahmed Latif, M.D. Michael Mbizo, M.D.
University of Washington/University of Nairobi, Mombasa, Kenya Principal Investigator: Joan Kreiss, M.D., M.S.P.H. Co-Investigators: J.O. Ndinya-Achola, M.D. Ludo Lavreys, M.D.
NIAID, 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.
NIAID press releases, fact sheets and other materials are available on the Internet via the NIAID home page at http://www.niaid.nih.gov.
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