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

Suppressive Therapy for Chronic Cytomegalovirus Infection

For chronic cytomegalovirus (CMV) infection, oral valganciclovir at a dose of 900 mg once daily is the recommended first-line suppressive therapy. 1

First-Line Suppressive Therapy Options

Oral Valganciclovir

• Dosage: 900 mg once daily with food 1
• Advantages:
  • Better bioavailability than oral ganciclovir 2
  • Convenient once-daily dosing improving compliance 2
  • Avoids complications related to intravenous access 2
• Dose adjustment: Required for renal impairment 3
  • CrCl 50-69 mL/min: 450 mg 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 following hemodialysis

Alternative Options

• Oral ganciclovir: 1000 mg three times daily with food 3
  • Less preferred due to lower bioavailability compared to valganciclovir 2
• Intravenous ganciclovir: 5 mg/kg daily 1
  • Reserved for patients unable to tolerate oral therapy
• Intravenous foscarnet: For ganciclovir-resistant CMV 1, 4
  • Requires strict monitoring of renal function and electrolytes
• Intravenous cidofovir: For multi-drug resistant CMV 1
  • Significant nephrotoxicity risk; requires probenecid pre-treatment

Duration of Suppressive Therapy

HIV-Infected Patients

• Traditionally recommended for life following CMV disease 1
• Consider discontinuation if:
  • CD4+ count increases to >100-150 cells/μL for >3-6 months on ART 1
  • HIV viral load is suppressed 1
  • No active CMV disease 1
• Restart suppressive therapy if CD4+ count decreases to <50-100 cells/μL 1

Transplant Recipients

• Duration depends on:
  • Type of transplant
  • Degree of immunosuppression
  • CMV serostatus (D+/R- at highest risk)
• Typically continued for 3-6 months post-transplant 5

Monitoring During Suppressive Therapy

Laboratory Monitoring

• Complete blood count: Weekly initially, then every 2 weeks 4
  • Monitor for neutropenia, thrombocytopenia, and anemia
• Renal function tests: Weekly 4
• CMV viral load: Every 1-3 months to assess for breakthrough infection 4

Clinical Monitoring

• For patients with CMV retinitis:
  • Regular ophthalmologic examinations 1
  • Patient self-assessment of visual acuity 1
• For other CMV disease:
  • Monitor for recurrence of symptoms

Special Considerations

Resistance Management

• Resistance should be suspected if:
  • Persistent or increasing viral load despite 2 weeks of appropriate therapy
  • Progressive clinical disease despite adequate treatment
• Options for resistant CMV:
  • Foscarnet (first option) 1, 4
  • Cidofovir (second option) 1
  • Combination therapy with ganciclovir and foscarnet for severe cases 1

CMV Colitis-Specific Management

• Initial treatment: IV ganciclovir 5 mg/kg twice daily for 3-5 days 1, 4
• Followed by oral valganciclovir 900 mg twice daily for 2-3 weeks 1, 4
• Then transition to maintenance dose of 900 mg once daily 4

Common Pitfalls and Caveats

1. Inadequate monitoring: Regular laboratory monitoring is essential to detect bone marrow suppression early.

2. Premature discontinuation: Stopping suppressive therapy too early can lead to disease recurrence, especially in severely immunocompromised patients.

3. Failure to adjust dose for renal impairment: Both valganciclovir and ganciclovir require dose adjustment in renal impairment to prevent toxicity.

4. Drug interactions: Be aware of potential interactions with other medications that may increase bone marrow suppression.

5. Resistance development: Long-term suppressive therapy carries risk of resistance development; monitor for clinical or virological breakthrough.

6. Inadequate hydration: Especially important with IV formulations to minimize renal toxicity.

7. Missed diagnosis of resistance: Failure to recognize drug resistance can lead to continued ineffective therapy and disease progression.