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 Zambia HIV National Guidelines
 


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 Guide Editors
 Editor In Chief
    Joel E. Gallant, MD, MPH

Pharmacology Editor
    Paul Pham, PharmD, BCPS

Zambia Guideline Team
   Peter Mwaba MMed PhD FRCP
   Alywn Mwinga MMed
   Isaac Zulu MMed MPH
   Velepie Mtonga MMed
   Albert Mwango MBChB
   Jabbin Mulwanda MMed FCS
 

 

 

Diagnosis>Opportunistic Infections>
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CMV, gastrointestinal

Khalil G. Ghanem, M.D.
02-20-2008

  • CMV is ubiquitous virus and considered endemic in Zambia, but limited data on epidemiology of CMV-related GI disease in Zambia.
  • Ability to make a definitive Dx of CMV-related GI disease challenging in Zambia due to limited endoscopy, Bx, and laboratory capacity.
  • In pt with CMV retinitis and clinical esophagitis or colitis, CMV is likely cause, especially if Sx unresponsive to empiric therapies for other pathogens.
  • None of typical treatments for CMV-related GI disease, besides HAART, are readily available in Zambia.
Zambia Information Author: Larry William Chang, MD, MPH

PATHOGENS

  • Cytomegalovirus (CMV): A herpesvirus; up to 60-100% seroprevalence; first peak in infancy (vertical + breastfeeding); second peak in young adults.
  • Transmitted vertically or via blood (lymphs and PMNs), saliva, milk, urine & sexual contact (cervical secretions and semen).
  • Establishes permanent latent infection in host.
  • Both primary and secondary infections (activation of latent infection or reinfection with another strain) occur. Most cases in immunosuppressed adults tend to be secondary infections.

CLINICAL

  • In HIV+ pts w/ low CD4 counts (<50), GI tract is the 2nd most common site of disease after eye.
  • Upper GI tract: commonly causes ulcers at lower esophageal sphincter, but can cause diffuse or more proximal esophagitis, gastritis, gastric ulcers, duodenitis, duodenal ulcers, and enteritis, including mesenteric vasculitis.
  • Lower GI tract: colon, perforations in ileum, rectal ulcers; manifestations range from no visibly apparent colitis to deep ulcers; most common finding is a mild, patchy colitis including vasculitis. Diarrhea usually accompanied by low-grade fever and abdominal pain, may see guaiac positive stools and fecal leukocytes.
  • Presence of GI involvement by CMV should prompt ophthalmologic evaluation for CMV retinitis.
  • Median survival after diagnosis is <10 mos without HAART. Imperative to begin HAART for immune reconstitution.

DIAGNOSIS

  • Esophagitis: endoscopy with Bx required in pts w/ odynophagia or dysphagia who fail to respond to empiric antifungal therapy.
  • Colitis: colonoscopic Bx when stool studies non-diagnostic; Bx necessary even if mucosa appears normal. Stool Cx for CMV not helpful.
  • Bx must show inflammation & CMV inclusion bodies. Cultures of biopsy material usually positive but nondiagnostic.
  • Tests to detect viremia (e.g. PCR or CMV antigenemia) have not been shown to predict active disease or recurrence (Wiselka MJ, Nicholson KG, Rowley S, et al.) in AIDS pts (unlike transplant pts).

TREATMENT

Antiviral Therapy

  • Valganciclovir 900mg po BID w/ food X3-4 wks (if GI symptoms don't interfere with meds); most data are in HIV+ w/ retinitis.
  • If patient unable to swallow, choice of ganciclovir (5mg/kg IV BID X3-4wks) vs. foscarnet (60mg/kg q8h or 90mg/kg q12h X3-4wks) should be dictated by toxicity profile of each drug.
  • Recent data indicate the disappearance of CMV inclusion bodies after 3 wks & complete healing after 6 wks of therapy.
  • No available data on the use of cidofovir for CMV GI tract disease.
  • HAART & immune reconstitution offer best hope for prevention of relapses.
Antiviral Resistance

  • Clinically resistant strains of CMV appear after prolonged periods of antiviral therapy, especially when treatment is interrupted or given at suboptimal doses.
  • Combination IV ganciclovir and IV foscarnet therapy may be attempted if monotherapy fails. (Whitley RJ, Jacobson MA, Friedberg DN, et al. & Salzberger B, Stoehr A, Heise W, et al.)

Drug Comments

DrugRecommendations/Comments
Cidofovir No data in CMV disease of GI tract, but would be expected to work.
Foscarnet Second-line therapy; main side effect is reversible (usually) renal dysfunction (hydration required) and electrolyte wasting.
Ganciclovir Used if PO valganciclovir cannot be used; main side effect is bone marrow suppression.
Valganciclovir Preferred in pts who can swallow; no data for use in CMV of GI tract in AIDS, although good results in CMV retinitis; excellent oral bioavailability.

FOLLOW UP

  • Maintenance therapy should be considered, particularly after reinduction for relapse (Whitley RJ, Jacobson MA, Friedberg DN, et al.)
  • Although limited efficacy data in this setting, oral valganciclovir may be the preferred agent in patients who can swallow; it may also be an agent used for maintenance (see above).

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