MUCOSAL INJURY AND DISRUPTION OF INTESTINAL BARRIER FUNCTION IN HIV-INFECTED INDIVIDUALS WITH AND WITHOUT DIARRHEA AND CRYPTOSPORIDIOSIS INNORTHEAST BRAZIL

Objectives: To determine the relative effects of AIDS-related diarrhea with or without cryptosporidiosis and microsporidiosis on intestinal function and injury. Methods: We studied 40 HIV-infected patients (20 with and 20 without diarrhea) and 13 healthy volunteers, using the dif ferential urinary excretion of ingested lactulose and mannitol as resp ective markers of barrier disruption and overall villous surface area. We also examined them for fecal leukocytes, lactoferrin, and alpha(1) -antitrypsin. Fasting subjects drank test solution containing lactulos e (5 g) and mannitol (1 g). Urine was collected for 5 h and tested for sugars by high-performance liquid chromatography with pulsed amperome tric detection. Results: HIV-positive patients with diarrhea had a 2.8 -fold higher lactulose:mannitol excretion ratio (L:M) than HIV-positiv e patients without diarrhea (p = 0.01) and 10.4-fold higher than healt hy volunteers (p = 0.004). This was accounted for by a 1.5- to 3.1-fol d higher rate of lactulose excretion by HIV patients with diarrhea tha n by those without diarrhea or by healthy volunteers. Mannitol excreti on was 32-55% less in patients with diarrhea than in those without dia rrhea or in healthy volunteers. Patients with cryptosporidial diarrhea had a nearly 6-fold higher L:M ratio than those without diarrhea (p < 0.001) and nearly 3-fold higher than those with non-cryptosporidial d iarrhea (p = 0.02). One patient with microsporidial infection had a ne arly 3-fold higher L:M ratio than controls without diarrhea. alpha(1)- Antitrypsin was positive in 40% of HIV-positive patients with cryptosp oridial infections and none of 12 HIV-positive patients with non-crypt osporidial diarrhea. Fecal lactoferrin or leukocytes were increased in all HIV patients with diarrhea. Conclusion: HIV infection is associat ed with intestinal dysfunction and injury, even in patients who do not have diarrhea. However, those with diarrhea, especially with cryptosp oridiosis or microsporidiosis, have even greater disruption of intesti nal barrier function with potentially important nutritional consequenc es.