GI DYSFUNCTION IN CHILDREN BORN TO HIV-INFECTED WOMEN

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Despite the rapidly increasing incidence of pediatric AIDS, little is known about the natural history of HIV infection in children, or the factors responsible for disease progression. Gastrointestinal dysfunction is a major component of the multisystem disease of children with AIDS. The gastrointestinal tract can be the target of malignancy, infection, and mucosal injury. As a result, vital immunologic and digestive processes are compromised and a vicious cycle of recurrent or prolonged diarrhea, malnutrition, and immunodeficiency may ensue. There is no prospective data regarding the incidence, etiology, or outcome of gastrointestinal dysfunction in children with HIV infection. Because of existing programs at the University of Maryland Hospital, we have a unique cohort of children born to women who are infected with the AIDS virus. This birth cohort will provide the basis for a longitudinal study of diarrhea and growth faltering. The aim of this project is to determine the relationship between diarrhea, poor growth, and the occurrence of enteric infection, immunologic dysfunction, diminished caloric intake, and nutrient malabsorption in children infected with HIV. Technology available at the Center for Vaccine Development will allow us to identify a comprehensive battery of enteropathogens, and to evaluate the role of pathogen-specific humoral and secretory immune responses in eradicating infection and preventing immune-mediated mucosal injury. Malabsorption of dietary sugars and fats will be detected noninvasively using serial growth and anthropomorphic measures, dietary histories, and analysis of selected nutrients in the blood. The children will be assessed routinely for evidence of immunologic disease. The value of gastrointestinal dysfunction as a predictor of clinical outcome will be determined. This information will provide the basis for designing subsequent studies to investigate the prevention and treatment of severe diarrhea and wasting in children with AIDS. Early interventions may alter disease progression, and will be helpful in decreasing morbidity and mortality associated with HIV infection.