Infection with GBV-C, a non-pathogenic flavivirus, appears to dramatically improve survival in HIV-infected adults. Eight of 10 studies to date found that GBV-C viremia reduced HIV-related mortality or improved therapeutic response; these results are unlikely artefactual. The mechanism by which GBV-C acts is unknown though GBV-C may inhibit HIV replication and alter cytokine and chemokine expression. We hypothesize that GBV-C infection also reduces mother-infant HIV transmission (which varies with HIV viral load) and slows HIV progression in children; neither have been previously examined. The Bangkok perinatal studies provide a unique opportunity to examine these issues. We propose to analyse sera of mothers and infants for GBV-C antibody and viral RNA from three CDC perinatal studies (a natural history and two clinical studies). The objectives of the proposed study are: 1. To determine if maternal GBV-C infection (RNA or antibody) reduces mother-infant HIV transmission; 2. To determine the association between GBV-C infection status and HIV status and biologic, behavioral and socio-economic variables; 3. To examine if GBV-C viremia is associated with slower progression to disease among HIV-infected infants; 4.To examine the rate of GBV-C mother-to-child transmission among HIV infected mothers as a function of maternal and delivery characteristics; and 5. to examine the timing of GBV-C clearance in mothers and infants. Extensive data and specimens from women and infants are available from the Thailand MOPH-CDC collaboration, including HIV serostatus and viral load, clinical, immunologic and hematologic measures, and demographic and behavioral variables. At CDC Atlanta, sera will be tested for antibody using a Roche assay, and for viral RNA with an in-house quantitative RT-PCR test. In women and children with GBV-C infection, later samples will be analyzed to determine the rate of clearance. Data will be analyzed through stratification, logistic regression, and Kaplan-Meier and Cox proportional hazards regression. As yet, much remains unknown about GBV-C, including its ability to reduce HIV transmission and slow HIV progression in children. The proposed study will provide important knowledge and may lend further credibility to the beneficial impact of GBV-C on HIV infection. A positive finding would add impetus to additional basic research to elucidate the biologic mechanisms and potentially develop new modatities of prophylaxis and treatment. [unreadable] [unreadable]