AIDS - Prevention
Developing safe and effective prevention strategies to curb
the human and economic costs of the HIV/AIDS pandemic has become an
international health priority. Toward this end, NIAID, which spearheads federal
funding for biomedical research on HIV/AIDS for the National Institutes of
Health (NIH), supports a broad-based HIV vaccine and prevention research
program.
NIAID's Division of AIDS (DAIDS) directs this program.
Institute staff meet regularly with scientific, public health and community
advisors to review the priorities and operation of the program.
The program has two main thrusts:
- to foster basic research on the structure and function of
HIV, vaccine formulations, vaccine delivery systems, laboratory studies of
vaccine performance and microbicides, and
- to promptly evaluate promising candidate vaccines,
microbicides and other intervention strategies in animal models and, if
warranted, in humans.
Traditional investigator-initiated research forms the
foundation for HIV/AIDS vaccine research. NIAID supports several special
collaborative and interdisciplinary initiatives to accomplish specific research
objectives.
- National Cooperative Vaccine Development Groups
(NCVDGs) constitute the core of preclinical HIV vaccine design and
evaluation efforts sponsored by NIAID. Teams of scientists from industry,
academia and government collaborate to develop and test novel experimental HIV
vaccine concepts in the laboratory and in animal models.
- The Cooperative Mucosal Immunology Group for
Investigations on AIDS Vaccines supports research on methods to
stimulate and evaluate mucosal immune responses to HIV and its monkey
counterpart, simian immunodeficiency virus (SIV). Investigators use this
information to design new vaccines that will protect against mucosal exposure to
HIV.
- The Antibody Serologic Project identifies and
standardizes panels of monoclonal antibodies to characterize the antigenic
components of HIV and SIV. This collaborative project involves investigators
from around the world.
- The HIV Variation Project examines the rates
and magnitudes of genetic and immunologic changes in HIV and related
retroviruses and their consequences for vaccine design. The project includes a
laboratory that determines the genetic sequences of large numbers of viral
isolates (Genetic Variation Contract), a laboratory to assess the immunologic
significance of genetic variation (Antigenic Variation Contract), and the HIV
Sequence Database and Analysis Unit at the Los Alamos National Laboratory,
which compiles and analyzes genomic sequences contributed by sequence
laboratories. The HIV Variation Project is carried out in collaboration with the
Centers for Disease Control and Prevention (CDC) and the World Health
Organization (WHO).
- Primate Research Laboratories answer
HIV-vaccine-related questions by testing HIV and HIV-like vaccines in
chimpanzees and monkeys. The Simian Vaccine Evaluation Units (S-VEUs)
evaluate vaccine concepts in the macaque model and compare immunologic and
protection data, permitting standardized and directly comparable evaluations of
various vaccine candidates. Substantial effort is being made to develop the
chimeric SIV-HIV (SHIV) model for use in challenge studies. The Chimpanzee
Unit, operated through an interagency agreement with the National Cancer
Institute, has been used to prepare chimpanzee stocks and to evaluate candidate
vaccine concepts and products in chimpanzees. The Immunology Laboratory
Support for Assessment of AIDS Vaccines in Primates (which includes several
contracts) develops, standardizes and performs cellular and serologic immune
assays to assess responses to SIV and HIV vaccines in the S-VEUs, and is also
available to NCVDG laboratories. This permits the direct comparison of candidate
vaccines evaluated in independent laboratories and facilitates selection of the
most promising vaccine designs.
- The Reagent/Resource AIDS Vaccine
Project acquires or produces biological and chemical
substances for comparative immunologic analyses, preclinical vaccine
development, adjuvant development and standardized immunologic assessments of
clinical samples from volunteers in vaccine trials.
- The Master Agreement for Preclinical HIV Vaccine
Development provides flexible resources for the preclinical evaluation
of the most promising HIV vaccine candidates. These resources include
preclinical evaluation of vaccines in nonhuman primates, vaccine production and
the development of reagents for preclinical and clinical vaccine
studies.
- The AIDS Vaccine Evaluation Group (AVEG)
conducts Phase I and Phase II trials in humans to evaluate the
safety of and immune responses stimulated by experimental HIV vaccines. AVEG
includes the following:
- A Vaccine Selection Group independently evaluates
the rationale and preclinical safety and immunogenicity data of candidate
vaccines prior to their study in AVEG trials.
- Six AIDS Vaccine Evaluation Units (AVEUs), located
at research centers throughout the United States, conduct Phase I and II
clinical trials of candidate HIV vaccines in volunteers who are not infected
with HIV.
- A Central Immunology Laboratory provides
state-of-the-art evaluation of antibody and cellular immune responses of
vaccinated volunteers in AVEG trials. Laboratory scientists evaluate samples
from the AVEUs using standardized assays, permitting the comparison of responses
in volunteers who receive different candidate vaccines at different AVEUs.
- A Mucosal Immunology Laboratory evaluates human
mucosal immune responses to candidate vaccines in standardized assays,
permitting the comparison of responses in volunteers who receive different
candidate vaccines at different AVEUs.
- A Data Coordinating and Analysis Center provides a
central facility for collecting and analyzing data from the trials conducted by
the AVEUs.
- A Data and Safety Monitoring Board periodically
reviews data from AVEG studies.
Planning for Efficacy Trials
NIAID is laying the groundwork for large-scale Phase III
efficacy trials of candidate HIV vaccines and other prevention strategies to
ensure that such trials begin promptly once suitable candidates are identified.
To assess the feasibility of conducting vaccine trials in
the United States, NIAID initially provided supplemental funds to help support
ongoing studies sponsored by the Centers for Disease Control and Prevention and
the National Institute on Drug Abuse, and to other investigators working with
populations at high risk of HIV infection.
To determine the feasibility of and develop the capability
for conducting such trials abroad, NIAID in 1992 awarded eight two-year
Preparation for AIDS/HIV Vaccine Evaluations (PAVE)
grants to U.S. researchers and their international collaborators.
In 1993 the NIAID unified and extended these efforts by
establishing the HIV Network for Prevention Trials
(HIVNET). HIVNET is charged with preparing for and conducting
large-scale, randomized, controlled trials to evaluate the efficacy of vaccines
and other strategies to prevent sexual, parenteral and perinatal transmission of
HIV. In addition, HIVNET provides a unique opportunity to study the epidemiology
of HIV transmission in different populations, and to examine the natural history
and pathogenesis of early HIV infection and disease. HIVNET consists of five
contracts:
- A domestic master contractor subcontracts with
clinical sites to conduct activities in preparation for efficacy trials. These
sites will evaluate the efficacy of HIV vaccines and other prevention strategies
in U.S. populations once suitable candidates are identified.
- An international master contractor subcontracts with
clinical sites to prepare for efficacy trials and to evaluate prevention
strategies in international populations.
- A statistical and data coordinating center provides
statistical and data management support for the domestic and international
trials.
- A central laboratory provides quality
assurance and specialized testing for the domestic and international trials, and
preparatory research trials.
- A specimen repository collects, stores and
distributes samples from the domestic and international clinical sites.
HIVNET investigators are collecting baseline data on virus
strains being transmitted, rates of new HIV infections and the prevalence of
other sexually transmitted diseases and other potential cofactors of HIV
transmission from various populations at high risk for HIV infection. They also
are collecting data on the willingness of high-risk individuals to enroll in
vaccine trials.
Several of the HIVNET sites are conducting randomized
controlled trials of various methods to prevent sexual and perinatal HIV
infection. These interventions include microbicides to prevent sexual
transmission, and antiretroviral drugs and HIV immune globulin to prevent
perinatal transmission. Behavioral interventions also are being
evaluated.
