Previous studies have documented the frequent occurence of malnutrition, nutrient malabsorption and mucous membrane injury in patients with AIDS. A striking feature was the lack of tissue repletion during apparent clinical stability. It is hypothesized that disease progression may result from a self-perpetuating cycle of immune deficiency leading to intestinal damage, malabsorption and malnutrition which causes further immune deficiency. Once established, the cycle can continue independently from the inciting agent (HTLVIII). Thus, proper treatment of AIDS would include nutritional rehabilitation and reestablishment of the mucous membrane's barrier to the environment. These studies will examine the causes and consequences of intestinal dysfunction and their response to treatment of the AIDS syndrome. Formal nutritional assessments will document the severity and course of malnutrition, its relationship to the timing of death and to the observed immune deficits. An intestinal perfusion study will be the cornerstone of the intestinal function studies and will assess salt and water absorption, intestinal permeability, and biliary and pancreatic secretions. A series of noninvasive techniques will be developed and validated against the results of the perfusion study. These tests, which will measure fat absorption, bile salt metabolism, bacterial overgrowth, pancreatic function, ileal function, and intestinal permeability, will be developed and used for longitudinal studies. Intestinal injury in AIDS will be further characterized and analyzed in relation to known infectious agents and noninfectious factors. The role of specific infectious agents in producing intestinal dysfunction will be delineated through longitudinal followup during treatment studies. Specific studies defining the interrelationships of Epstein-Barr virus and HTLVIII infections in the intestines will be performed through a contractual arrangement with Dr. David Volsky of the University of Nebraska. Finally, studies will begin to assess the effects of antiviral therapy, treatment with intravenous gammaglobulin, and indomethacin on nutritional status and intestinal function. The results of these studies should provide important information concerning the mechanisms of disease progression in AIDS and begin to delineate the strategies that will be needed to treat this disease effectively.
Showing the most recent 10 out of 36 publications
