This proposal continues to reflect the objectives of the Women and Infants Transmission Study, a prospective natural history cohort study of HIV positive pregnant women and their offspring which began in the field in 1989. From demonstrated accrual, forty eight to seventy pregnant HIV - infected women will be enrolled annually so that forty eight available infants will be born into the study annually and studied prospectively. It will (l) continue the evaluation of maternal-infant HIV transmission including the timing of transmission. In addition to the existing core protocol, a proposal to examine the extent of maternal infant transfusion at the time of delivery by determining HLA of maternal and fetal leukocytes by PCR and search for the presence of the noninherited maternal HLA alleles in fetal blood using allele specific priming is included. In addition, a proposal to determine the relevance of MHC genetics to vertical-transmission of HIV is included. Available surgical specimens will be examined for HIV and correlated with maternal risk factors for transmission to ascertain timing of transmission. (2) Assess promising early diagnostic techniques to rapidly identify HIV infected infants. (3) Examine the natural history of these infants in an era of antiretroviral, prophylactic and immune based therapy which includes the identification of infants at risk for rapid HIV progression. This proposal includes a study examining maternal and infant CTL responses to HIV determinants as a predictor for transmission of disease and rapid progression of disease in infants. Additional objectives include the impact of pregnancy on the natural history of HIV infection - a study best performed in that small subset of women accumulated over the time of the whole study who become pregnant after being. enrolled in the study. This population will allow for examination of the prepregnant immunological and virological status of the subject. A survey to examine the acceptability of a vaccine trial among pregnant women at risk for transmission is proposed and a pilot is presented. The core study utilizes standardized interview, standardized clinical examination, neurological examination and psychological testing, NIAID certified virologic and flow cytometric measurements, toxicology and pathology to meet the research goals.
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