Lisa A. Spacek, MD, PhD and Khalil G. Ghanem, MD, PhD
- CMV is ubiquitous virus and considered endemic in Zambia, but limited data on epidemiology of CMV-related disease in Zambia.
- Most studies demonstrate higher prevalence of CMV antibody in Africans compared to persons in developed world.
- In contrast, limited reports suggest that prevalence of CMV-related disease in Africa lower than in developed world, possibly due to death prior to development of CMV disease.
- Capacity to make definitive Dx of GI, neurological, and pulmonary CMV limited in Zambia.
- Dx of CMV retinitis can be made by dilated fundoscopic examination by experienced observers.
- None of typical treatments for CMV disease, besides HAART, are readily available in Zambia.
Zambia Information Author: Larry William Chang, MD, MPH
- Member of human herpesvirus beta subfamily w/ envelope & dsDNA; viral DNA polymerase is target for drugs. Latency established after infection. Transmission via saliva, blood, genital secretions, breast milk, urine, or feces. Reactivation (increasing w/ advancing immune suppression) responsible for most HIV-related disease.
CMV retinitis: Full-thickness necrotizing retinitis, most common manifestation of CMV in pts w/ AIDS.
CMV, gastrointestinal: EGD w/ Bx for esophagitis; colonoscopy with Bx for colonic disease; Dx defined by clinical Sx, macroscopic mucosal lesions on endoscopy, and CMV by Cx, histopathology, immunohistochemical analysis, or in situ hybridization. Histology reveals large basophilic intranuclear "owl's eye" and intracytoplasmic inclusion bodies.
CMV, neurologic: CSF WNL for encephalitis, but in polyradiculomyelitis often w/ PMNs, mildly increased protein levels & low glucose. Most sensitive is PCR of CSF for CMV; Cx usually +; MRI may show characteristic periventricular white matter changes (encephalitis).
CMV pneumonitis: Uncommon condition. Positive Cx from BAL does not establish Dx. Both clinical Sx (see below) & Bx results demonstrating viral inclusions must be used together for Dx.
- Up to 50% of pts w/ AIDS developed CMV disease in pre-HAART era; ~32% developed CMV retinitis.
Retinitis: Painless loss of vision, decreased acuity, floaters, flashing lights, leading to retinal detachment. Lesions yellow-white fluffy (peripheral lesions sometimes granular) retinal infiltrates w/ areas of hemorrhage. Progression leads to atrophic gliotic scar. Immediate ophtho consult if CD4 <100 and ocular symptoms or other CMV-related disease.
GI: fever, nausea, odynophagia, dysphagia, & substernal chest pain w/ esophagitis; diarrhea, abdominal cramps, weight loss w/ colitis; hepatitis also occurs. Colonic mucosal hemorrhage with perforation can be life-threatening complication.
Neurological: dementia, ventriculoencephalitis, or ascending polyradiculomyelopathy; progressive bilateral leg weakness, areflexia, & urinary retention w/ radiculomyelitis; lethargy, confusion, fever, ataxia, & cranial nerve abnormalities w/ encephalitis.
Pulmonary: Uncommon. Fever, SOB, diffuse pulmonary infiltrates, & no other infection that could account for these Sx (up to 50% of pts w/ PCP will have positive CMV Cx from bronch specimens: requires Rx only for PCP).
- Primary infection: mononucleosis-like syndrome w/ fever, lymphadenopathy, & hepatitis.
- Eyes: retinitis.
- GI tract: esophagitis; colitis; gastritis; pancreatitis (less common); cholecystitis (less common); hepatitis.
- Nervous system: encephalitis; radiculomyelitis; mononeuritis multiplex; myelitis.
- Lungs: pneumonitis.
- CV: myocarditis.
- Hematologic: thrombocytopenia & hemolytic anemia.
- Most cases of CMV disease due to reactivation of latent infection (up to 70% of adults seropositive; up to 90% of MSM seropositive).
- Best approach for prevention is initiating ART before CD4 <200.
- If CD4 count <100, yearly ophthalmological exams mandatory.
- Any ophthalmological complaint in pts w/advanced immunosuppression requires immediate ophthalmologic consultation.
- Preemptive therapy in pts w/ advanced immunosuppression in absence of organ system involvement not recommended.
- Preemptive diagnostics on urine, stool, & BAL fluid (i.e. CMV antigenemia or quantitative PCR) do not correlate with future disease course.
- See individual modules (retinitis, GI, & neurological) for specific details & alternate therapies.
- Choice of therapy should be guided by side-effect profile of each drug.
Retinitis: intraocular ganciclovir implant q 6 mos (if no immune reconstitution) + valganciclovir 900 mg PO twice-daily x14-21d then 900 mg po once-daily w/ food. Systemic Rx may prevent contralateral involvement.
GI: ganciclovir 5 mg/kg IV twice-daily x3-4 wks OR foscarnet 60 mg/kg IV q12h OR valganciclovir 900 mg PO twice-daily x3-4 wks w/ food if Sx not interfering w/ oral intake
Neurological: In general, poor response to Rx. Ganciclovir 5 mg/kg IV twice-daily + foscarnet 90 mg/kg IV q12h x3-6 wks, followed by maintenance combination Rx. ART is most effective.
- Pneumonitis: ganciclovir 5 mg/kg IV twice-daily x3-4 wks OR foscarnet 90 mg/kg IV q12h OR valganciclovir 900 mg PO twice-daily x3 wks
- In retinitis, GI disease and pneumonitis, no data demonstrate adverse effect from ART initiation, and immediate treatment with ART recommended. In neurologic disease, delay of ART may be prudent but not data-based.
Ganciclovir: neutropenia, thrombocytopenia, & catheter-related toxicities.
Valganciclovir: neutropenia & thrombocytopenia.
- Foscarnet: nephrotoxicity, neurotoxicity, nausea, genital ulceration & catheter-related complications.
- Cidofovir: nephrotoxicity, neutropenia, uveitis, hypotony.
- Immune recovery vitritis assoc. w/ ART has been reported & can be treated w/ systemic or periocular steroids (Kempen, JH, 2006).
- Resistance most likely to develop w/ prolonged under-dosing of antivirals.
- Mutations in the CMV UL97 phosphotransferase gene confer variable ganciclovir resistance. Mutations in UL97 and UL54 genes confer high-level resistance to ganciclovir and cross-resistance to cidofovir.
- Cross-resistance less likely between ganciclovir and foscarnet (although cases have been reported).
- If no response to therapy, resistance testing can be performed by specialized labs; turn around time usually 10-14d.
||Some of the toxicities are irreversible; no data for use in neurological disease.
||Electrolyte, renal & neuro toxicities most common.
||PO form has poor bioavailability and has been replaced by valganciclovir; bone marrow toxicity most common.
||Excellent PO bioavailability; published studies for retinitis in pts w/ AIDS. Generally drug of choice for first-line Rx in pts who can take PO.
- Clinical response to therapy most useful indicator.
- Limited data on utility of serum markers (CMV antigenemia or quantitative PCR) in monitoring response to therapy or predicting recurrent disease.
- ART is necessary adjunct to CMV-specific therapy. Short-term mortality for pts without immune reconstitution is very high.
- Centers for Disease Control and Prevention ;
Guidelines for prevention and treatment of opportunistic infections in HIV-infected adolescents and adults. ;
2009 ; Vol.
58 ; pp.
Basis for recommendation
Available at: http://www.cdc.gov/mmwr/pdf/rr/rr58e324.pdf
Comments:OI guidelines from CDC, NIH, and HIVMA of the IDSA released March 24, 2009