National Institute of Allergy and Infectious Diseases–NIAID finances the largest portfolio of AIDS-related basic research of all the NIH institutes. NIAID's basic research goals are to examine HIV entry mechanisms, cell types (host and virus), reservoirs, and latency; study the mechanisms of cellular immunity; assess the role of autoimmunity in AIDS pathogenesis; research the role of other viruses as cofactors in AIDS; understand HIV gene regulation; define the viral components responsible for infectivity, syncytia formation, CD4 receptor binding, and immune response elicitation; and determine the mechanism of T-cell killing.
NIAID's AIDS-related basic research is conducted in many venues, including universities, independent laboratories and research centers, and its intramural laboratories. The Pathogenesis Branch in NIAID's Division of AIDS (DAIDS) administers most of the institute's AIDS basic research grants. Its mission is “to discover the mechanisms by which HIV causes immune deficiency, produces other pathological disorders, and avoids immune surveillance” (NIAID, 1990). The branch's extramural grants support research on the biological properties, molecular biology, and host response to HIV infection and on the development of an animal model for HIV infection. The branch administers Programs of Excellence in Basic Research on AIDS (PEBRA), which are five-year grants to support clusters of long-term investigations of biological processes related to AIDS. PEBRAs were awarded to five sites in 1988.
DAIDS also funds nine centers for AIDS research using core grants to investigators who have a record of proven excellence in AIDS research and are already receiving NIH funds. The grants provide core support for central research and support services and also include some money for salaries for junior-level investigators and for renovation and upgrading of facilities. Intramurally, NIAID's researchers are conducting a range of research on the nature of the etiologic agent (HIV) and its pathogenesis in addition to a considerable program of vaccine and drug development studies. Selected research includes studies focused on the immunopathogenic mechanisms of HIV infection and opportunistic infections, animal retroviruses, and how the CD4 receptor recognizes the HIV envelope protein.
National Cancer Institute–NCI supports the next largest basic AIDS research program at NIH, much of it intramural. Its efforts focus on HIV and the mechanisms of pathogenesis, including the following major areas: regulation of HIV gene expression, the mechanism of HIV infection, virus cofactors in pathogenesis, regulation of the CD4 receptor, mechanisms of loss of T-helper cell immune function, processing of HIV proteins, the role of cytokines and immunity in HIV pathogenesis, and research on the structural biology of HIV for the purpose of devising therapeutic agents.
National Institute of Neurological Disorders and Stroke–NINDS supports the third largest NIH program of basic AIDS research, the primary goal of which is understanding the relationship between HIV and the human nervous system. NINDS-supported research falls into two main scientific areas: how HIV damages nervous system cells and how it crosses the blood-brain barrier. In support of these research endeavors, NINDS funds both extramural and intramural basic research. Extramural research focuses on HIV subtypes that enter the brain, methods to improve the transport of drugs into the central nervous system, and the role of metabolites in the pathogenesis of AIDS dementia. In contrast, intramural research examines a number of key scientific questions including SIV neurologic disease, analysis of the effect of HIV gene products on nervous system cells, the pathogenic mechanism of AIDS dementia, and differentiation of HIV-and zidovudine (AZT)-induced neuropathies.
National Heart, Lung, and Blood Institute–NHLBI conducts a wide range of AIDS research from the very basic to the clinical, focusing on the cardiac, pulmonary, and hematologic consequences of HIV infection. The institute's basic AIDS research includes the following major areas: chronic processes of cardiac and pulmonary pathology in AIDS, HIV-related viruses, the pathogenesis of cardiac and respiratory problems unique to the pediatric population, the HIV disease process in the lung (particularly to understand cell injury caused by Pneumocystis carinii