What is the treatment for cytomegalovirus (CMV) infection?

Treatment of Cytomegalovirus (CMV) Infection

The first-line treatment for cytomegalovirus infection is valganciclovir orally or ganciclovir intravenously, with the choice depending on the severity of infection, ability to absorb oral medication, and renal function. 1

First-Line Treatment Options

Valganciclovir (Oral)

• Induction therapy: 900 mg twice daily for 21 days 1
• Maintenance therapy: 900 mg once daily following induction 1
• Preferred for patients who can tolerate oral medications and have adequate gastrointestinal absorption 2
• Rapidly absorbed and converted to ganciclovir, providing systemic exposure comparable to IV ganciclovir 3

Ganciclovir (Intravenous)

• Dosage: 5 mg/kg every 12 hours for 14-21 days followed by maintenance therapy 2
• Preferred for severe infections, particularly in patients with impaired gastrointestinal absorption 2
• Major side effect is myelosuppression (anemia, neutropenia, thrombocytopenia) 2
• Dose reduction may be necessary in up to 40% of patients due to hematologic toxicity 2

Treatment Selection Algorithm

1. Assess infection severity:

   • For severe, disseminated, or sight-threatening CMV disease: Start with IV ganciclovir 2
   • For less severe disease with intact GI function: Oral valganciclovir is appropriate 2

2. Evaluate renal function:

   • Dose adjustment required for both medications in patients with renal impairment 1
   • For patients on hemodialysis (CrCl <10 mL/min): Valganciclovir should not be used 1

3. Consider specific organ involvement:

   • For CMV retinitis: Induction with either valganciclovir or ganciclovir, possibly combined with intraocular implant for sight-threatening lesions 2
   • For CMV encephalitis: Combination therapy with ganciclovir and foscarnet is recommended 2

Second-Line Treatment Options

Foscarnet (Intravenous)

• Dosage: 60 mg/kg every 8 hours or 90 mg/kg every 12 hours for 14-21 days 2
• Used for ganciclovir-resistant CMV infections or when ganciclovir is not tolerated 2
• Main toxicity is decreased renal function; up to 30% of patients experience increased serum creatinine 2
• Can cause serious electrolyte imbalances (calcium, phosphorus, magnesium, potassium) 2

Cidofovir (Intravenous)

• Alternative for resistant infections 2
• Limited by nephrotoxicity and poor penetration of the blood-brain barrier 2

Combination Therapy

• Combination of ganciclovir and foscarnet may be beneficial for:
  • CMV retinitis that has relapsed on single-agent therapy 2
  • Sight-threatening disease 2
  • CMV encephalitis (74% improvement or stabilization reported in HIV patients) 2

Duration of Treatment

• Treatment should continue until CMV is no longer detectable by PCR 4
• For CMV retinitis in HIV patients: Lifelong maintenance therapy is typically required 2
• For transplant patients: Duration depends on the type of transplant and risk factors 2

Monitoring During Treatment

• Weekly monitoring of CMV viral load by PCR 4
• Regular complete blood counts to monitor for myelosuppression 2
• Renal function tests to assess for nephrotoxicity 2
• Ophthalmologic examinations for patients with or at risk for CMV retinitis 2

Special Populations

Transplant Recipients

• Preemptive therapy or prophylaxis is often used in high-risk transplant recipients 2
• Letermovir is approved for prophylaxis in adult CMV-seropositive allogeneic hematopoietic cell transplant recipients 2

HIV Patients

• CMV retinitis requires aggressive treatment and maintenance therapy 2
• Immune recovery with effective antiretroviral therapy is an important component of management 2

Congenital CMV

• Ganciclovir (6 mg/kg IV every 12 hours for 6 weeks) has been evaluated in symptomatic congenital CMV disease 2
• Treatment resulted in more rapid resolution of liver enzyme abnormalities and less hearing loss 2

Common Pitfalls and Caveats

• Delayed initiation of therapy can lead to worse outcomes; prompt treatment is essential 2
• Myelosuppression from ganciclovir may require dose modification or use of granulocyte colony-stimulating factor 2
• Drug resistance can develop with extended use, particularly in severely immunocompromised patients 2
• Renal toxicity requires careful monitoring and possible dose adjustments for both ganciclovir and foscarnet 2

By following this treatment approach and carefully monitoring for efficacy and toxicity, CMV infection can be effectively managed in most patients, reducing morbidity and mortality associated with this opportunistic pathogen.