Diarrhea and wasting are relatively common features of AIDS. The cause of gastrointestinal dysfunction may be opportunistic infections (including chronic viral, mycobacterial or parasite infections), bacterial overgrowth, or an immune regulatory defect resulting in systemic stimulation from luminal antigens. Prior studies from our laboratory have been designed to detect enteric pathogens in patients with AIDS and patients at risk for HIV infection. The results showed that about half of AIDS patients with diarrhea had a likely enteric pathogen, the most common being cryptosporidia. The present proposal represents an extension of our prior work with an attempt to characterize """"""""AIDS enteropathy"""""""" defined as diarrhea and wasting in the absence of a recognized enteric pathogen. This proposal takes advantage of new collaborative opportunities for studies of epidemiology, immunology, pathology and gastroenterology. The AIDS clinic will serve as the source of clinical material. Three funded projects permit systematic evaluations at six month intervals of 2000-3000 patients/year with HIV infection including 200-300 with AIDS. These patients will serve as the cohort for longitudinal studies to define the incidence and prevalence of diarrhea and wasting. The results will be correlated with disease stage, risk category and immunological assessment. Patients who have the """"""""diarrhea wasting syndrome"""""""" will undergo microbiological studies using selective techniques based on our prior work. Patients with no likely enteric pathogen using noninvasive techniques will be classified as """"""""AIDS enteropathy"""""""". The major project is designed to define the morphology and immunopathology of the gut in patients with """"""""AIDS enteropathy"""""""". A broad goal will be to determine if AIDS enteropathy is a discrete entity that can be ascribed to HIV infection or consequences of a superimposed process such as a viral, mycobacterial or parasitic infection that is not detected with noninvasive screening tests. This work will include patients with diarrhea-wasting as defined above and controls without diarrhea who are matched for disease stage. The studies will include: 1) ultrastructural changes, 2) studies for microbial agents using electron microscopy, special stains, in situ hybridization, and culture and 3) studies of immunopathology including possible autoimmune features and 4) comparisons of circulating and secretory immunoglobulin.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK040618-02
Application #
3241016
Study Section
Diabetes and Digestive and Kidney Diseases Special Grants Review Committee (DDK)
Project Start
1988-07-15
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Belitsos, P C; Greenson, J K; Yardley, J H et al. (1992) Association of gastric hypoacidity with opportunistic enteric infections in patients with AIDS. J Infect Dis 166:277-84
Bartlett, J G; Belitsos, P C; Sears, C L (1992) AIDS enteropathy. Clin Infect Dis 15:726-35
Greenson, J K; Belitsos, P C; Yardley, J H et al. (1991) AIDS enteropathy: occult enteric infections and duodenal mucosal alterations in chronic diarrhea. Ann Intern Med 114:366-72
Guyer, D R; Jabs, D A; Brant, A M et al. (1989) Regression of cytomegalovirus retinitis with zidovudine. A clinicopathologic correlation. Arch Ophthalmol 107:868-74