Treatment of Severe Cytomegalovirus (CMV) Infection in Immunocompromised Patients
For severe CMV infection in immunocompromised patients, the recommended treatment is combination therapy with ganciclovir (5 mg/kg intravenously every 12 hours) and foscarnet (60 mg/kg intravenously every 8 hours or 90 mg/kg intravenously every 12 hours) for 3 weeks, followed by maintenance therapy. 1
First-Line Treatment Options
Severe CMV Disease (Including Encephalitis)
- Combination therapy: Ganciclovir (5 mg/kg IV every 12h) + Foscarnet (60 mg/kg IV every 8h or 90 mg/kg IV every 12h) for 3 weeks 1
- This regimen has shown improvement or stabilization in 74% of patients with CMV encephalitis or myelitis in HIV-infected patients
- Followed by maintenance therapy after initial treatment period
Less Severe CMV Disease
- Intravenous ganciclovir: 5 mg/kg twice daily for 2-3 weeks 2
- Oral valganciclovir: 900 mg twice daily to complete a 2-3 week course (after initial IV therapy) 2, 3
- FDA-approved for treatment of CMV retinitis in AIDS patients and prevention of CMV disease in transplant recipients 3
Treatment for Specific Populations
Transplant Recipients
- Intravenous ganciclovir followed by oral valganciclovir is the standard first-line treatment 4
- Treatment should be coupled with strategies to minimize immunosuppression when possible 4
- Weekly monitoring of CMV replication by PCR or pp65 antigen detection is recommended to guide therapy 1
HIV/AIDS Patients
- For CMV retinitis: Induction with valganciclovir 900 mg orally twice daily for 21 days, followed by maintenance with 900 mg once daily 3
- For CMV encephalitis: Combination therapy as described above 1
Second-Line Options for Treatment Failures or Drug Resistance
Ganciclovir Resistance or Intolerance
- Foscarnet: 90 mg/kg twice daily for 2-3 weeks 2
- Similar efficacy to ganciclovir with lower incidence of treatment-limiting side effects in transplant patients 1
Refractory Cases
- Cidofovir: Use is limited by significant nephrotoxicity (approximately 25%) 1, 2
- Poor response rate in pre-emptive settings (only 1 out of 21 patients showed sustained response in one study) 1
Monitoring During Treatment
- Weekly CMV viral load monitoring 2
- Liver function tests twice weekly initially, then weekly 2
- Complete blood count (monitor for neutropenia, thrombocytopenia) 2, 5
- Renal function tests (especially with foscarnet or cidofovir) 2
- Consider CSF PCR at the end of therapy in CNS disease to confirm clearance 1
Special Considerations
Pediatric Patients
- Combination therapy may be a safe alternative to monotherapy in high-risk infants with primary immune deficiency syndromes and high viral loads 5
- Toxicity is common in pediatric patients receiving combination therapy, with neutropenia, thrombocytopenia, and electrolyte abnormalities being the most frequent adverse events 5
Potential Complications and Pitfalls
Drug toxicities:
Resistance development:
Late CMV disease:
- Can occur after completion of prophylaxis or treatment 7
- Requires continued monitoring, especially in severely immunocompromised patients
Treatment Duration and Follow-up
- Minimum treatment duration of 2-3 weeks 2
- Continue treatment until clinical improvement and satisfactory decline in viral load 4
- For CNS disease, consider longer treatment duration (3 weeks minimum) 1
- Consider maintenance therapy in patients with ongoing immunosuppression 1
Importance of Immunologic Recovery
- When feasible, reduction of immunosuppression should be part of the treatment strategy 1, 4
- This approach is crucial for durable control of CMV infection 4
- For HIV patients, combination with HAART has shown efficacy in some patients with CMV encephalitis 1
The treatment of severe CMV infection in immunocompromised patients requires aggressive antiviral therapy, careful monitoring, and management of immunosuppression. Combination therapy with ganciclovir and foscarnet provides the best outcomes for severe disease, while less severe manifestations may be managed with single-agent therapy.