Our preliminary data on the biology of HIV-2 suggest that this virus may have a distinct biology from HIV-1. It is relevant, therefore, to assess these differences in populations infected with significant rates of both HIV-2 and HIV-1. Senegal is such a West African country and the collaboration already established with investigators there provides a strong base for future research. The prolonged incubation period for HIVs in general suggests that much can be learned from the evaluation of infected individuals over time. This would include: 1) the dynamics and risk factors for transmission, 2) the immune response parameters evaluated over the course of infection and their correlation with viral burden and clinical course and 3) the evolution of HIV pathogenesis. Thus, natural history studies of HIV viruses in general will provide the richest source of information on risks for transmission, course of infection and evolution of disease. At present, the transmission and natural history of HIV-2 in pediatric populations are areas in need of further study. Project 1 will seek to provide important information on risk factors and the rate of perinatal transmission of HIV-2 in direct comparison to HIV-1. We will explore various antibody and DNA markers of infection for both early diagnosis and prognostic markers and correlate these with clinical course and outcome in perinatally infected infant. Project 3 will provide more information on HIV in pediatric groups by evaluating prevalence and disease association in children at high risk for exposure to the virus. In this sentinel group survey we hope to learn more about the risk factors for HIV infection in children. This project will also provide valuable information on the natural history of HIV-2 infection in older children. Since HIV disease evolution would be expected to progress more rapidly in pediatric populations, Projects 1 and 3 will also contribute to our understanding of the comparative pathogenic potentials of HIV-2 and HIV-1. This will be concurrently addressed in the proposed studies of Project 2. This will study disease evolution with HIV in adults by first surveying all AIDS-like disease presentations and evaluating for the strength of association with HIV-1 and HIV-2. By following infected individuals over time we hope to study the clinical course of HIV-2 and HIV-1 disease from initial presentation and evaluate immunologic and serologic parameters that may be of prognostic value. The full characterization of HIV-2 infection in these populations should provide the basis for evaluating therapeutic and preventative strategies in the future.