NATURAL HISTORY OF VERTICALLY TRANSMITTED HIV INFECTION

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Risk factors for development of symptomatic AIDS in infants remains unclear. Several studies have suggested that although some infected children born to seropositive mothers develop symptoms and die by age two, others have a stable course over several years. Methodologic problems such as the inability to identify infected children at birth due to the presence of maternal antibody, small sample size and complications due to parental IV drug abuse have hampered ascertainment of predictors of poor outcome in children of seropositive mothers. We propose to study the natural history of HIV-1 infection in children infected at or before birth. Children born to seropositive mothers will be followed prospectively and the possible role of risk factors such as maternal symptomatology during pregnancy, mode of delivery, presence of neutralizing antibody and intact delayed-type hypersensitivity will be assessed. We intend to study children born to seropositive mothers in Rwanda, where HIV-1 is endemic; preliminary data indicate 5-15% seropositivity. Infected children will be identified at birth by detection of the viral genome in peripheral blood using polymerase chain reaction (PCR). Children of the first 200 infected women will be followed prospectively for three years; children of 100 non-infected women will be followed in parallel. Clinical and laboratory examinations including assays of viral expression will be performed periodically to assess progression of disease, HIV-1 infection, and immune status (cellular and serologic). Histories of intercurrent infections, injections and immunizations will be collected at each visit. Time to development of symptomatic AIDS/ARC or death will be analyzed as a function of the risk factors discussed above. The identification of factors associated with poor outcome and an improved understanding of the association of viral expression and disease progression should allow better management of pediatric AIDS patients.