What is the recommended suppressive therapy for chronic Cytomegalovirus (CMV) infection?

Suppressive Therapy for Chronic CMV Infection

The recommended suppressive therapy for chronic cytomegalovirus (CMV) infection is oral valganciclovir 900 mg once daily, which should be continued lifelong unless immune reconstitution occurs. 1

First-Line Suppressive Therapy Options

Oral Valganciclovir

• Dosage: 900 mg once daily with food 2
• Advantages:
  • Convenient once-daily dosing
  • Superior bioavailability compared to oral ganciclovir 3
  • Avoids complications related to intravenous access 3

Alternative Options

• Oral Ganciclovir: 1000 mg three times daily with food 4
• Intravenous Ganciclovir: 5 mg/kg once daily 1
• Intravenous Foscarnet: 90-120 mg/kg once daily 1
• Intravenous Cidofovir: Used for resistant cases 1

Duration of Suppressive Therapy

Immunocompromised Patients (HIV/AIDS)

• Continue suppressive therapy lifelong unless immune reconstitution occurs 1
• Consider discontinuation if:
  • CD4+ T-lymphocyte count increases to >100-150 cells/μL for >3-6 months on antiretroviral therapy 1
  • HIV viral load is suppressed 1

Transplant Recipients

• Duration depends on transplant type and risk factors:
  • Kidney transplant: Continue for at least 3 months post-transplantation 1
  • Heart/kidney-pancreas transplant: Continue for at least 100 days post-transplantation 1, 2
  • High-risk patients (D+/R-): Consider longer duration 2

Dose Adjustments

Renal Impairment

Adjust dose based on creatinine clearance:

• CrCl 50-69 mL/min: 450 mg once daily
• CrCl 25-49 mL/min: 450 mg every 2 days
• CrCl 10-24 mL/min: 450 mg twice weekly
• CrCl <10 mL/min: 450 mg three times per week after hemodialysis 4

Monitoring During Suppressive Therapy

• Complete blood count: Weekly for the first month, then monthly 1
• Renal function: Monthly 1
• CMV viral load: Every 3 months or with unexplained symptoms 1
• For patients with CMV retinitis: Regular ophthalmologic examinations 1

Management of Breakthrough CMV Infection

If CMV reactivates during suppressive therapy:

1. Reinduction therapy with IV ganciclovir 5 mg/kg twice daily for 2-3 weeks 1
2. Consider resistance testing
3. For resistant cases, switch to:
   • Foscarnet 60 mg/kg IV every 8 hours 1
   • Consider combination therapy with ganciclovir and foscarnet for severe cases 1

Special Considerations

Drug Resistance

• More common with prolonged therapy
• Options for resistant CMV:
  • Foscarnet (first alternative) 1
  • Cidofovir 1
  • Maribavir for refractory cases 1, 5

Toxicity Management

• Neutropenia: Consider dose reduction or G-CSF support 1
• Renal toxicity: Ensure adequate hydration, especially with foscarnet 1
• Electrolyte abnormalities: Monitor and replace as needed, particularly with foscarnet 1

Pitfalls and Caveats

• Oral ganciclovir has poor bioavailability and is not recommended for induction therapy 6
• Acyclovir and valacyclovir are ineffective for CMV prophylaxis or treatment 1
• Valganciclovir should always be taken with food to maximize absorption 2
• Patients with gastrointestinal issues may have reduced absorption of oral medications; consider IV therapy 1
• Never abruptly discontinue suppressive therapy without confirming immune reconstitution 1
• Regular monitoring is essential as CMV can develop resistance during long-term suppressive therapy

By following these evidence-based recommendations for suppressive therapy, the risk of CMV reactivation and disease can be significantly reduced in chronically infected patients.