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 Zambia HIV National Guidelines
 


Introduction  

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Sexually Transmitted Infections (STIs)  

General Principles of Antiretroviral Therapy for Chronic HIV Infection in Adults and Adolescents  

When to Start ARV Therapy for Chronic HIV Infection in Adults and Adolescents  

Initial Regimen for ARV Therapy  

Adherence  

Baseline evaluation and Monitoring  

Calculations: Ideal Body Weight, Body Mass Index and Creatinine Clearance  

ARV Therapy for Individuals with Tuberculosis Co-Infection  

Adverse Effects and Toxicity  

Immune Reconstitution Inflammatory Syndrome (IRIS)  

Changing or Stopping ART  

Treatment Failure  

Stopping ARV Therapy  

Post Exposure Prophylaxis  

Cotrimoxazole Prophylaxis  

WHO Staging in Adults and Adolescents  

Nutrition Care and Support  

Palliative Care in HIV and AIDS  

 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
 

 

 

Pathogens>Viruses>
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Cytomegalovirus

Lisa A. Spacek, MD, PhD and Khalil G. Ghanem, MD, PhD
04-27-2009

Zambia Specific Information

  • 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

MICROBIOLOGY

  • 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.

CLINICAL

  • 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).

SITES OF INFECTION

  • 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.

TREATMENT

Prevention

  • 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.
Antiviral therapy: Induction

  • 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.
Antiviral therapy: Maintenance phase

Treatment-related side effects

Resistance

  • 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.

Drug Comments

DrugRecommendations/Comments
Cidofovir Some of the toxicities are irreversible; no data for use in neurological disease.
Foscarnet Electrolyte, renal & neuro toxicities most common.
Ganciclovir PO form has poor bioavailability and has been replaced by valganciclovir; bone marrow toxicity most common.
Valganciclovir 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.

FOLLOW UP

Monitoring

  • 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.

OTHER INFORMATION

  • ART is necessary adjunct to CMV-specific therapy. Short-term mortality for pts without immune reconstitution is very high.

Basis for Recommendations

  • Centers for Disease Control and Prevention ; Guidelines for prevention and treatment of opportunistic infections in HIV-infected adolescents and adults. ; MMWR ; 2009 ; Vol. 58 ; pp. 55-60 ;
    Rating: Basis for recommendation
    Note: 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

REFERENCES

REFERENCED WITHIN THIS GUIDE


 
Diagnosis
 


Complications of Therapy


Malignancies


Miscellaneous


Opportunistic Infections


Organ System

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Antimicrobial Agents


Antiretrovirals


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Guidelines
 


Zambia HIV National Guidelines

Management
 


Antiretroviral Therapy


Laboratory Testing


Miscellaneous

Pathogens
 


Bacteria


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