What is the treatment for Cytomegalovirus (CMV) infection?

Treatment of Cytomegalovirus (CMV) Infection

For CMV infection treatment, oral valganciclovir, IV ganciclovir, IV foscarnet, or IV cidofovir are all effective options, with the choice depending on the site of infection, severity, and patient factors. 1

Treatment Algorithm Based on Site of Infection

CMV Retinitis

1. For immediate sight-threatening lesions (adjacent to optic nerve or fovea):

   • Preferred: Ganciclovir intraocular implant plus oral valganciclovir (AI) 1
   • Some ophthalmologists recommend initial intravitreous ganciclovir injection at diagnosis for immediate high local concentration until implant can be placed (CIII) 1

2. For small peripheral lesions:

   • Oral valganciclovir alone (900 mg twice daily for induction, then once daily for maintenance) (BII) 1
   • Even in ART-naïve HIV patients with small peripheral lesions, systemic anti-CMV therapy for 3-6 months until immune recovery is beneficial (BII) 1

CMV Colitis or Esophagitis

• IV ganciclovir or foscarnet for 21-28 days or until symptoms resolve (BII) 1
• Oral valganciclovir may be used if symptoms are not severe enough to interfere with absorption (BII) 1
• For CMV colitis specifically: IV ganciclovir 5 mg/kg twice daily for 3-5 days followed by oral valganciclovir 900 mg twice daily for 2-3 weeks 1

CMV Pneumonitis

• If CMV is confirmed as the cause of pulmonary dysfunction by histology or cytology:
  • Treatment with IV ganciclovir, foscarnet, or cidofovir is recommended, although limited data exist on outcomes (CIII) 1

CMV Neurological Disease

• Prompt initiation of therapy is critical for optimal response
• Combination treatment with ganciclovir and foscarnet may be preferred as initial therapy to stabilize disease (BII) 1
• This approach has substantial adverse effects; optimal treatment with ART optimization is not established 1

Dosing Recommendations

Valganciclovir (Oral)

• Induction therapy: 900 mg (two 450 mg tablets) twice daily for 21 days 2
• Maintenance therapy: 900 mg once daily 2
• Take with food to increase bioavailability 2
• Adjust dose for renal impairment 2

Ganciclovir (IV)

• Induction: 5 mg/kg every 12 hours for 14-21 days 1
• Maintenance: 5 mg/kg daily 1
• For pediatric patients: 5 mg/kg/dose twice daily for 14-21 days 1

Foscarnet (IV)

• 60 mg/kg every 8 hours or 90 mg/kg every 12 hours for 14-21 days 1
• Administer slowly (no faster than 1 mg/kg/minute) 1
• Infuse with saline fluid loading to minimize renal toxicity 1

Special Considerations

HIV-Infected Patients

• Initiate appropriate antiretroviral therapy (ART) for patients with acute CMV retinitis, gastrointestinal disease, or pneumonitis (BIII) 1
• For neurological disease, consider delaying ART until clinical improvement occurs to avoid inflammatory reactions (CIII) 1
• Best prevention of CMV disease is maintaining CD4+ count >100 cells/μL through effective ART 1

Monitoring

• For CMV retinitis: Indirect ophthalmoscopy through dilated pupil at diagnosis, after completion of induction therapy, 1 month after initiation, and monthly thereafter while on anti-CMV treatment (AIII) 1
• Monthly fundus photographs using standardized technique provide optimal follow-up 1
• For patients with immune recovery, ophthalmologic follow-up can decrease to every 3 months 1

Adverse Effects

• Ganciclovir/Valganciclovir: Neutropenia, thrombocytopenia, anemia, renal dysfunction 1
• Foscarnet: Nephrotoxicity, electrolyte abnormalities (calcium, phosphorus, magnesium, potassium), seizures, cardiac dysrhythmias 1
• Cidofovir: Nephrotoxicity, neutropenia, metabolic acidosis 1

Treatment Advantages of Valganciclovir

• Oral valganciclovir has 60% bioavailability compared to only 6-9% for oral ganciclovir 3, 4
• Provides systemic exposure similar to IV ganciclovir 5
• Convenient once-daily dosing improves patient compliance 4
• Avoids complications related to IV access and hospitalization 4, 6
• Cost-effective compared to IV therapy 4

Pitfalls and Caveats

1. Drug resistance: Extended use of antiviral agents can lead to resistance, particularly in patients with prolonged exposure 7
2. Toxicity monitoring: Regular monitoring of complete blood counts and renal function is essential during treatment 1
3. Renal adjustment: All anti-CMV drugs require dose adjustment in renal impairment 2
4. Drug interactions: Be aware of potential interactions with immunosuppressants and other medications
5. Treatment duration: Premature discontinuation can lead to relapse; continue until adequate immune recovery when possible 1

Remember that the best prevention of CMV disease is immune reconstitution through effective ART in HIV patients or appropriate management of immunosuppression in transplant recipients.