The increasing numbers of infants that are infected by HIV-1 infection necessitates the design of effective intervention strategies. However, it will first be necessary to develop and evaluate sensitive methods to detect HIV-1 infection in newborns at birth or shortly after. In addition, more definitive information is needed regarding the role of breast milk, maternal viral load, and maternal and infant HIV-1 neutralizing antibody in the vertical transmission of HIV-1. This study will evaluate a number of different assays performed on specimens from two existing Ugandan cohorts consisting of approximately 775 HIV-1 antibody positive and 225 HIV- antibody negative maternal-infant pairs. The proposed study has the following specific aims: 1. Determine whether the maternal viral burden and/or serum beta-2 microglobulin correlate with HIV-1 vertical transmission and clinical outcome of the infant using the following assays: quantitative total serum HIV-1 P24 antigen, quantitative HIV-1 PCR, serum beta-2 microglobulin. 2. Determine the relationship of the maternal and infant humoral immune response to viral isolates prevalent in the population and in specific maternal-infant pairs using a viral isolate neutralization assay and gp120 V3 loop antibody assays. 3. Determine the sensitivity/specificity of several laboratory assays [HIV- 1 p24 antigen (free and dissociated, HIV-1 culture, HIV-1 PCR, HIV-1 IgA antibody and assay) and clinical assays (BCG scar and PPD induration) to detect HIV-1 infection and predict clinical outcome in the newborns of infected mothers. 4. Determine the role of breast milk in HIV-1 transmission by correlating presence of detectable HIV-1 in breast milk and transmission. These investigations may yield important advances in early detection of HIV-1 and in understanding the role of immunity in HIV-1 vertical transmission. This health related project will also enhance the potential of Uganda as a site for vaccine and chemotherapy trials.
