PATHOGENESIS OF INTESTINAL DYSFUNCTION IN AIDS

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Intestinal dysfunction is an important cause of morbidity and mortality in individuals with HIV infection. Intestinal disease is particularly a problem in infants and young children due to the central role of the gastrointestinal tract in growth and development and as a portal of entry of infectious pathogens. The pathophysiology of the intestinal dysfunction has not been delineated. Possible factors contributing to gastrointestinal dysfunction and malnutrition in HIV-infected individuals include opportunistic gastrointestinal infections with bacterial, viral or parasitic pathogens, chronic diarrhea due to intestinal colonization with aerobic or anaerobic bacteria, malabsorption of ingested nutrients due to acquired deficiencies in intestinal enzymes, and/or direct intestinal infection with HIV. We propose to perform a prospective, cohort-design evaluation of intestinal function in infants perinatally infected with HIV. We will obtain detailed nutritional and anthropometric data on the study children and on control children matched for age and socio-economic status. We will also perform detailed virological, parasitological, and bacteriological analyses of their stools and intestinal tissue and attempt to correlate intestinal infections with HIV and other pathogens with gastrointestinal dysfunction. We will utilize the results of these analyses to develop and evaluate interventions for the prevention and treatment of intestinal dysfunction in the study children. The successful control of intestinal diseases might result in a significant reduction in the morbidity and mortality associated with HIV infections in children and adults.