Malabsorption is impaired uptake of nutrients from the intestines. Nutrients are normally absorbed from food in the intestines by cells that make up the finger-like villi lining the intestinal wall. Certain disease processes-including HIV infection can cause the villi to become atrophied and shortened. This cell malfunction results in impaired absorption of nutrients.

Diarrhea occurs at some point in the clinical course of most people with AIDS or HIV infection. It may occur early on or in end-stage infection, and may be sporadic or continuous. Diarrhea is a major source of mortality in HIV-infected children in Africa (Thea et al.); HIV-infected Zairian infants have an 11-fold increased risk of dying from diarrhea compared with uninfected infants.

The GI symptoms of AIDS were originally attributed to opportunistic enteric pathogens or to malignancy. Smith et al. report that specific pathogens can be isolated in the majority of patients. Grohmann et al. detected viruses in 35% of fecal specimens from 65 HIV-positive patients with diarrhea compared to only 12% of specimens taken at the same time from 65 HIV-positive patients without diarrhea. Patients with diarrhea were more likely to have astrovirus, picobirnavirus, caliciviruses and adenoviruses. However, Ullrich et al. suggest that abnormalities of the intestinal lining can also result from HIV infection itself.

The gastrointestinal tract can be affected by many types of infectious agents:

Parasitic diseases:
 - Cryptosporidiosis
 - Isosporiasis
 - Microsporidiosis
 - Entameba histolytica and Giardia lamblia 
  (both respond to conventional treatment).

Viral infections:
 - Cytomegalovirus. Colitis is the most commonly
   recognized GI manifestation of CMV disease in AIDS

Bacterial infections:
 - Mycobacterium avium complex (MAC).
 -  Salmonellosis
 - Campylobacter and chronic Shigella dysentery present
   with symptoms similar to those of salmonellosis.
   Standard treatments are effective. High rates of
   Clostridium difficile-associated diarrhea resulting from
   antibiotic therapy have been reported as well.

Treatment Results:
Tiemey et al. treated 9 HIV-positive patients with chronic diarrhea and no enteric pathogens with 5-ASA (Mesalamine) 6 g/day PO. Diarrheal symptoms improved in 7/9 patients, and rectal p24 content was significantly reduced over 2 months. No side effects were reported.

A randomized, double-blind, placebo-controlled trial of octreotide acetate (Sandostatin) in 129 HIV-positive patients with refractory diarrhea. Patients were randomized to receive octreotide acetate (100 µg SC three times daily) or placebo. No significant differences between the treatment group and control group were reported. At three weeks, 46% of the octreotide acetate group reported a 30% decrease in stool volume, versus 36% of the patients in the placebo group (NS). In an open-label extension of the trial, all patients received octreotide acetate 500 µg SC three times daily. Patients from the previously randomized arms reported a decrease in stool volume during the open-label extension; 42% and 39%, respectively.

Cello et al. enrolled 51 patients with HIV-related wasting in an open-label, dose-escalating study of octreotide acetate (Sandostatin) (50, 100, 250, 500 µg SC three times daily). 21/51 patients (41.2%) had a complete response (reduction in daily stool volume by 50% or reduction to <250 mL/d). 14/21 responders (67%) had no identifiable pathogens at initial screening compared to 9/30 (30%) nonresponders (P  < 0.01). Reduction in stool volume from baseline was associated with doses higher than 50 µg. Side effects included burning at injection site, nausea and vomiting. Octreotide acetate may inhibit pancreatic secretion, but this side effect is manageable with pancreatic enzyme replacement therapy.

A phase I trial of diethylhomospermine (DEHSPM), a polymine analog, is under way for refractory AIDS-related diarrhea.

REFERENCES:
Cello et al. Effect of octreotide on refractory AIDS-associated diarrhea. Ann Int Med 115: 705-10, 1991.

Grohmann 0 et al. Enteric viruses and diarrhea in HIV-infected patients. NEJM 329(i):14-20, 1993.

Simon DM et al. Multicenter trial of octreotide in patients with refractory acquired immunodeficiency syndrome-associated diarrhea. Gastroenterology 108:1753-60,1995.

Smith PD, moderator. Gastrointestinal infections in AIDS. Ann Int Med 116: 63-77,1992.

Thea DM et al. A prospective study of diarrhea and HIV-1 infection among 429 Zairian infants. NEJM 329:1696-702, 1993.

Ullrich R et al. Small intestinal structure and function in patients infected with human iniinunodeficiency virus (HIV): evidence of HIV-induced enteropathy. Ann Int Med 111: 15-21, 1989.

OTHER REPORTS:
Chlebowski R et al. Nuritional status, gastrointestinal dysfunction, and surival in patients with AIDS. J Gastro 84: 1288-93, 1989.

Connolly G et al. Non-cyptosporidial dirrhea in human immunodeflciency virus (HIV) infected patients. Gut 2: 195-200, 1989.