We propose to address 3 central issues in vertical transmission of HIV-1 infection from mother to child. These issues are: l) occurrence of vertical transmission of HIV-1 from 25-30% of infected pregnant women to their offspring but lack of transmission to the majority of these offspring; 2) the widely variable pace of HIV-1 -related disease progression in children; and 3) timing and route of transmission from mother to child.
We aim to investigate the roles of HIV-1 nucleotide sequence diversity and neutralization of HIV-1 quasispecies in vertical transmission and disease progression and to study the timing and route of vertical transmission from mother to child. We plan to analyze serial blood specimens from our established cohort of infected pregnant women and mother-child pairs in NY and NJ who reflect the racial and ethnic distribution of AIDS in the U.S.
We aim to: 1) Determine the nucleotide sequences of portions of the HIV-1 envelope (V1, V3, V4, C4) by using PCR amplification of uncultivated peripheral blood mononuclear cells (PBMCs) and plasma. We will measure the degree of diversity present within specimens at each time point and determine the change in diversity. over time; 2) Utilize sequence data obtained from pregnant women and their infected offspring at different time points and from different fluid compartments as well as virologic, immunologic, and clinical data to investigate the timing and route of vertical transmission; 3) Quantitate HIV-1 cultured from PBMCs and plasma by limiting dilution and determine the relationship between the degree of diversity and viral load within single patient specimens; 4) Study neutralization of HIV-1 quasispecies by assaying sera from mother and child. We shall examine neutralization of quasispecies in virus cultivated from mother and child and shall determine the sequence of portions of env (V1, V3, V4, C4) of viruses which are neutralized and those that escape neutralization; and 5) Correlate molecular, viral, and neutralization data with the occurrence of vertical transmission and pace of disease progression in children.
