Infection with HIV-1 usually results in a gradual deterioration of the immune system. Many studies have searched for markers that predict HIV-1 progression. Pharmacologic interventions can then be instituted earlier with decrease in morbidity and prolongation of life expectancy. To our knowledge no such studies have specifically evaluated a Hispanic or Puerto Rican population. We propose a five-year prospective longitudinal clinical trial to evaluate immunological and virological markers of disease progression in a Hispanic population. One-hundred-twenty-four patients with HIV-1 infection in a CDCP stage A1 will be consecutively enrolled into the study. The patients will be followed every three months in the RCRII Center. HIV-l clinical manifestations will be identified and recorded. A selected profile of T lymphocyte subsets counts will be measured by flowcytometry each patient visit. By evaluating the clinical findings and CD4+ T cell counts, progression into more advanced CDCP stages will be documented. Once progression of HIV-infections is documented further immunological and virological studies will be performed. PBMC's will be obtained from HIV-infected patients and stimulated with PHA in vitro for 14 days. At the end of the culture period p-24 Ag will be measured and T lymphocyte subsets determined by flowcytometry. Cytotoxicity of PBMC lymphocytes against acutely HIV-l infected CD4+ cells will be measured in a CR-51 release assay. Measurement of secreted lL-2 and lFN-gamma associated with stabilization of the immune system and non-progression of HIV-l infection will be done. Likewise levels of lL-4, IL-10 and TNF-alfa, associated with immune deterioration and disease progression will be determined. Release of the putative cytokine cellular antiviral factor (CAF) by PBMC will be evaluated. In selected patients cloning of CD4+ and CD8+ cells will be attempted. Polyantigenic immunomodulator (PAI) has been reported to preferentially induce the release of lL-2, IFN-gamma and TNF alfa over lL-4 and IL-10. In order to test the possibility of in vitro immune restoration by PAI, PHA stimulated PBMG's will be cultured in the presence of PAI and differences in patterns of lymphocyte subsets and cytokine secretion studied. As a result of this proposed study valuable information will be derived that will foster better management of HIV-infected patients.
