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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI021414-03
Application #
3131517
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1986-07-01
Project End
1989-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
St. Luke's-Roosevelt Institute for Health Science
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10019
Maia, Bruno S; Engelson, Ellen S; Wang, Jack et al. (2005) Antiretroviral therapy affects the composition of weight loss in HIV infection: implications for clinical nutrition. Clin Nutr 24:971-8
Engelson, E S; Kotler, D P; Tan, Y et al. (1999) Fat distribution in HIV-infected patients reporting truncal enlargement quantified by whole-body magnetic resonance imaging. Am J Clin Nutr 69:1162-9
Kotler, D P; Rosenbaum, K; Wang, J et al. (1999) Studies of body composition and fat distribution in HIV-infected and control subjects. J Acquir Immune Defic Syndr Hum Retrovirol 20:228-37
Kotler, D P (1999) Characterization of intestinal disease associated with human immunodeficiency virus infection and response to antiretroviral therapy. J Infect Dis 179 Suppl 3:S454-6
Kotler, D P; Shimada, T; Snow, G et al. (1998) Effect of combination antiretroviral therapy upon rectal mucosal HIV RNA burden and mononuclear cell apoptosis. AIDS 12:597-604
Kotler, D P; Fogleman, L; Tierney, A R (1998) Comparison of total parenteral nutrition and an oral, semielemental diet on body composition, physical function, and nutrition-related costs in patients with malabsorption due to acquired immunodeficiency syndrome. JPEN J Parenter Enteral Nutr 22:120-6
Clayton, F; Snow, G; Reka, S et al. (1997) Selective depletion of rectal lamina propria rather than lymphoid aggregate CD4 lymphocytes in HIV infection. Clin Exp Immunol 107:288-92
Kotler, D P; Burastero, S; Wang, J et al. (1996) Prediction of body cell mass, fat-free mass, and total body water with bioelectrical impedance analysis: effects of race, sex, and disease. Am J Clin Nutr 64:489S-497S
Kotler, D P; Grunfeld, C (1995) Pathophysiology and treatment of the AIDS wasting syndrome. AIDS Clin Rev :229-75
Kotler, D P; Giang, T T; Thiim, M et al. (1995) Chronic bacterial enteropathy in patients with AIDS. J Infect Dis 171:552-8

Showing the most recent 10 out of 36 publications