AIDS enteropathy: occult enteric infections and duodenal mucosal alterations in chronic diarrhea OBJECTIVE: To investigate occult enteric infections and morphologic changes in the small intestine in patients with advanced human immunodeficiency virus (HIV) infection and chronic diarrhea of undefined cause. DESIGN: Case-control study. SETTING: Referral-based clinic and hospital in tertiary care center. PATIENTS: Twenty-two patients with advanced HIV infection (19 with the acquired immunodeficiency syndrome [AIDS], 3 with AIDS-related complex) with chronic diarrhea, selected because of previously negative stool evaluations for bacterial or parasitic pathogens, were compared with 13 patients with advanced HIV infection (9 with AIDS, 4 with AIDS-related complex) without diarrhea by analysis of endoscopic biopsies using light and electron microscopy, viral culture, and morphometric studies. Both groups were convenience samples and had at least 7 months follow-up. MEASUREMENTS AND MAIN RESULTS: Eleven of twenty-two patients with HIV infection and chronic diarrhea but only 1 of 13 patients without diarrhea showed occult enteric pathogens (that is, undetected by routine studies) after extensive evaluation of duodenal and colorectal biopsies. Mycobacterium avium-intracellulare and microsporidia were the most common occult agents in study patients with diarrhea (5 each). Patients with diarrhea and occult enteric infections had greater weight loss (mean, 14.3 kg compared with 6.2 kg; P less than 0.05) and shorter survival (1 of 11 compared with 8 of 11 still alive; P less than 0.004) than those with diarrhea but no identified pathogens (defined as "AIDS enteropathy"). Duodenal morphometry showed decreased villus-to-crypt ratios because of villus atrophy and crypt elongation in HIV-infected patients both with and without diarrhea compared with normal controls (P less than 0.001 for each). All three groups showed comparable frequencies of epithelial mitoses. CONCLUSIONS: Further endoscopic biopsy evaluation of patients with AIDS who had unexplained chronic diarrhea showed an occult infectious cause in half of the cases. However, altered villus and crypt architecture in advanced HIV infection was independent of the presence of diarrhea or enteric infection and therefore did not correlate with AIDS enteropathy. Subnormal epithelial proliferation in response to injury could be a factor, but the underlying cause of the architectural changes remains obscure. We suggest that T-cell dysfunction may play a role. 