HIV IN MOTHERS AND INFANTS--IMMUNITY AND EARLY DIAGNOSIS

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We propose to assess maternal factors associated with maternal-infant HIV transmission in Haitian and U.S. women. We will determine the quantity and form of latent and actively replicating HIV and determine the relationship with the maternal immune response to HIV and the probability of maternal-infant transmission. Quantitative Polymerase chain reaction - Enzyme immunoassay (PCR-EIA) will be developed to quantify genomic mRNA, and singly and double spliced mRNA to determine the form of HIV genetic material in maternal peripheral blood and umbilical cord blood. We have determined the genetic sequence from 21 infected Haitian adults and determined the consensus sequence for our population. Peptides from the principle neutralizing domain (PND) will be made to determine the contribution of antibodies against epitopes other than those from the PND to overall neutralizing activity. Furthermore, we will measure the ADCC capacity of maternal sera, viral specific cytotoxic T-lymphocytes (CTL), and the level of CD4 and CD8 positive cells to determine if the level of immune responsiveness is associated with maternal viral load or maternal-infant transmission. To identify HIV infected infants under 8 weeks of age we will evaluate novel PCR assays for DNA and RNA, anti-HIV IgA, and p24 antigenemia following acid hydrolysis HIV induced T-cell proliferation, and specific CTL responses at birth, 1 to 2 months of age and at 3 to 6 months of age. The timing of these responses in infants will be used to estimate what proportion of infants were infected before and at the time of birth. These investigations will take advantage of stored specimens available from more than 250 HIV seropositive mothers of uninfected infants, 50 mothers of infected infants, and two ongoing cohort studies that enroll more than 150 infants born to seropositive women a year.