Diagnosis>Opportunistic Infections>

PATHOGENS

• A member of the Betaherpesviridae, double-stranded DNA virus; up to 60-100% seroprevalence. Most infections asymptomatic, virus shed in absence of Sx. Severe disease seen in fetus,  AIDS, and immunosuppressed.
• Transmitted vertically, sexually or by close contact (family members, daycare) via blood , tears, saliva, breast milk, urine, cervical secretions and semen.
• Establishes permanent latent infection in host.
• Both primary and secondary infections (reactivation of latent infection or reinfection with another strain) occur. Most cases in immunosuppressed adults tend to be reactivation.

CLINICAL

• In HIV, CD4 usually <50. GI tract is 2nd most common site of disease after eye.
•  In AIDS, esophagitis accounts for 5-10% of CMV disease, with fever and odynophagia; also causes gastritis, gastric ulcers, duodenitis, duodenal ulcers, enteritis, and mesenteric vasculitis.
• In AIDS, colitis accounts for 5-10% of CMV disease, with fever, weight loss, abdominal pain, hematochezia, and diarrhea (guaiac + stool and fecal leukocytes). Complications include perforation and hemorrhage; most common finding is a mild, patchy colitis including vasculitis.
• CMV in GI tract should prompt ophthalmologic exam for  CMV retinitis.
• Median survival after Dx is <10 mos without ART.
• Begin ART 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.
•  CMV GI disease defined by clinical Sx, findings of macroscopic mucosal lesions on endoscopy, and demonstration of CMV in Bx specimen. Intranuclear "owl's eye" inclusions have surrounding halo and marginated chromatin.
• Tests to detect viremia (e.g. PCR or CMV antigenemia) have not been shown to predict active disease or recurrence. CMV viral load has poor positive predictive value, but reasonable negative predictive value for disease.
• Treatment of viremia in absence of organ system involvement not recommended.

TREATMENT

• Valganciclovir 900 mg po twice-daily w/ food x 3-4 wks (if GI symptoms don't interfere with meds); most data are in HIV+ w/ retinitis.
• If pt unable to swallow, choice of ganciclovir (5 mg/kg IV twice-daily x 3-4wks) vs. foscarnet (60 mg/kg q8h or 90 mg/kg q12h x 3-4wks) according to toxicity profile of each drug.
• Recent data indicate disappearance of CMV inclusion bodies after 3 wks and complete healing after 6 wks of therapy.
• No available data on the use of cidofovir for CMV GI tract disease.
•  Initiate or optimize ART. Chronic maintenance CMV therapy not recommended, may consider for relapse.
• DHHS OI treatment guidelines available at: http://aidsinfo.nih.gov/contentfiles/Adult_OI.pdf

• Drug resistance occurs after prolonged periods of antiviral therapy, when treatment is interrupted or given at suboptimal doses, and with persistent high-level viral replication.
• Combination IV ganciclovir and IV foscarnet therapy may be attempted if monotherapy fails.
• Mutations in UL97 gene confer variable resistance to ganciclovir. Combined mutations in UL97 and UL54 confer high-level resistance to ganciclovir and cross-resistance to cidofovir. Less commonly, UL54 mutation may confer ganciclovir-foscarnet cross-resistance.

Drug Comments

Basis for Recommendations

• NIH, CDC and HIVMA/IDSA ; Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents ; June 18, 2008 ; Vol. 84-91 ;
  Rating: Basis for recommendation
  Note: Available at: http://aidsinfo.nih.gov
  Comments:Updated OI treatment guidelines
  
  
• Whitley RJ, Jacobson MA, Friedberg DN, et al.; Guidelines for the treatment of cytomegalovirus diseases in patients with AIDS in the era of potent antiretroviral therapy: recommendations of an international panel. International AIDS Society-USA.; Arch Intern Med; 1998; Vol. 158; pp. 957-69;
  ISSN: 0003-9926;
  PUBMED: 9588429
  Rating: Basis for recommendation
  Comments:Guidelines for treatment of CMV in era of HAART. Authors stress that although epidemiological features of CMV disease are changing because of HAART, continued attention must be paid to CMV disease in HIV+ pts to prevent irreversible endorgan damage.
  
  

REFERENCES

REFERENCED WITHIN THIS GUIDE

• Cytomegalovirus