11. Diarrhea in Patients with HIV

Definition

  • Chronic diarrhea: 3+ loose or liquid stools per day for more than 4 weeks.
  • Pre-ARV era: 40-80% of patients with HIV have diarrhea due impact of HIV on GI tract. The majority of CD4+ T cells reside on mucosal surfaces, where they form a major target for HIV in early infection. Loss of gut mucosal CD4 cells causes mucosal damage, increased translocation across bowel.

Etiology

Infectious causes of diarrhea:

Pathogens

Examples

Bacteria
  • Individuals with HIV are at risk for same pathogens as patients without HIV, but have greater risk of prolonged and invasive disease (nontyphoid Salmonellae (NTS) risk up to 300-fold higher, campylobacter incidence 39 times higher)
  • E. coli, Shigella, C. difficile, LGV (ulcerative retrocolitis, fistulizing bubo in the rectum)

Mycobacteria
  • Risk of MTB, NTMB disseminated infections increases with progression of HIV
  • Disseminated MAC (in advanced HIV)

Parasites
  • Giardia lamblia, Entamoeba histolytica, Blastocystis hominis, Strongyloides stercoralis
  • Spore forming protozoa: Isospora belli, cryptosporidium parvum, cyclospora cayetanensis

Fungi
  • Microsporidia, disseminated dimorphic fungi (histoplasmosis)

Viruses
  • HIV (especially during 0-6 weeks of initial seroconversion)
  • HIV enteropathy: jejunal villous atrophy, crypt hyperplasia
  • CMV (colitis +/- hematochezia, weight loss, fever, abdominal pain). Greatest risk in CD4 <50

Non-infectious causes of diarrhea:

  • Diarrhea is a common side effect of ART.
  • HIV-associated gastrointestinal malignancy: KS (regardless of CD4 count), lymphoma, anal cancer/other GI cancer.
  • HIV can impair pancreatic exocrine function, causing impaired fat absorption and chronic diarrhea.

Evaluation

  • History (travel, sexual ROS, camping, etc.).
  • Updated CD4 count, viral load (much higher suspicion if CD4 <200).
  • Stool examination:
    • 3 separate stool samples, best if only 1 per day over a 10 day period.
    • Microscopy: O/P, trichrome stain (microsporidia), acid fast stain (crypto, cyclospora, isospora) bacterial culture, C. diff assay, specific virology and protozoal PCR (e.g., BioFire).
    • Consider LGV nucleic acid amplification test from anal swabs (contact DPH).
    • Serum viral PCR for disseminated CMV infection, MAC blood cultures, serum CrAg, histoplasma Ag.
  • If pathogen negative, consult GI for flex sig. Endoscopy yields an additional diagnosis in 30-70% of pathogen-negative cases.
    • Biopsy for histology, standard and mycobacterial culture, CMV PCR; can also test for EBV (lymphoproliferative disease) and HHV8 (Kaposi’s). Next step may be colonoscopy and/or imaging.
    • CMV colitis often detected endoscopically (most common AIDS-associated CMV is actually retinitis – 70% of cases).
  • Radiology: usually nonspecific, but certain patterns can help narrow differential (CT with oral and IV contrast).

Management

  • Patients with undetectable VL and high CD4s who have acute diarrhea can be managed with volume repletion and close follow-up.
  • If infectious cause found, treat accordingly.
  • Supportive agents: antimotility agents (once C. diff is ruled out), adsorbents, cholestyramine.
  • Start or optimize ARV, review all drugs and withdraw any that may be causative (consult with HIV specialist before changing ARV regimens).
  • Consider nitaxozanide in cryptosporidiosis – esp. if CD4 <180 (patients with well-controlled HIV usually have self-limited disease).
  • Crofelemer is an FDA approved drug that blocks chloride channels on the luminal membrane of enterocytes in the GI tract to reduce efflux of sodium and water, which in turn reduces the frequency and consistency of diarrhea in patients with HIV (ADVENT study) -- 17% of patients with remission vs. 8% in placebo group.

 

Dikman, AE et al. HIV-Associated Diarrhea: Still an Issue in the Era of Antiretroviral Therapy. Dig Dis Sci. 2015; 60(8):2236-45

Feasey NA, Healey P, Gordon MA. Review article: the aetiology, investigation and management of diarrhea in the HIV-positive patient. Aliment Pharmacol Ther, 2011 Sep; 34(6):587-603.

Flanigtan T et al. Cryptosporidium infection and CD4 counts. Ann Int Med. 1992;116(10):840

Macarthur RD et al. Efficacy and safety of crofelemer for noninfectious diarrhea in HIV-seropositive individuals (ADVENT trial): a randomized, double-blind, placebo-controlled, two-stage study. HIV Clin Trials. 2013 Nov-Dec;14(6):261-73.