HIV-1 infection leads to impairment of certain critical immune functions in persons with AIDS. The immunosuppression manifests as increased susceptibility to opportunistic organisms and development of certain neoplasms. Since this immunosuppression is often out of proportion to the magnitude of the depletion of T helper cells and since monocytes are involved in host defense against many of the opportunistic infections, it is important to investigate the role of HIV-1 induced monocyte dysfunction in AIDS pathogenesis. Preliminary evidence indicates that monocytes infected with replicating HIV-1 in vitro are unable to phagocytize and /or kill certain pathogens such as T. gondii and C. albicans, two opportunistic agents that frequently cause life- threatening disease and/or morbidity in AIDS patients. In light of these potentially relevant preliminary findings, it is important to pursue the significance and the mechanism of this defect by: 1) examining the impact of HIV-1 infection in patients on the ability of macrophages to contain opportunistic pathogens in the target organs; 2) determining whether HIV-1 infection is directly responsible for the mononuclear phagocyte abnormalities in vitro; and 3) isolating mononuclear phagocytes from infected patients to directly assay their microbicidal activity and/or infection with HIV. These approaches will require both patient materials obtained at autopsy and/or biopsy and in vitro analyses.
