What is the recommended treatment for Cytomegalovirus (CMV) infection?

Treatment of Cytomegalovirus (CMV) Infection

Intravenous ganciclovir at 5 mg/kg twice daily for 14-21 days is the first-line treatment for serious CMV disease, including disseminated infection and CMV retinitis, with transition to oral valganciclovir 900 mg twice daily after clinical improvement for less severe cases. 1, 2

Initial Treatment Selection by Disease Severity

Serious CMV Disease (Tissue-Invasive, Disseminated, or Life-Threatening)

• All serious CMV disease requires intravenous ganciclovir 5 mg/kg twice daily for 14-21 days as the mandatory initial therapy 2, 1
• Serious disease includes CMV retinitis, pneumonitis, gastrointestinal disease with severe symptoms, encephalitis, and any disseminated infection 2, 1
• For CMV encephalitis specifically, combination therapy with ganciclovir (5 mg/kg IV every 12 hours) plus foscarnet (60 mg/kg IV every 8 hours or 90 mg/kg every 12 hours) for 3 weeks is recommended to maximize response despite higher toxicity 2

Mild to Moderate CMV Disease in Adults

• After 3-5 days of IV ganciclovir, transition to oral valganciclovir 900 mg twice daily is appropriate if clinical improvement is observed and oral absorption is adequate 1, 3
• Complete the full 14-21 day course with the combination of IV followed by oral therapy 1, 3

Pediatric Patients

• All CMV disease in children must be treated with intravenous ganciclovir only—oral valganciclovir is not approved for treatment in pediatric patients 2
• The dose is 5 mg/kg IV every 12 hours for 14-21 days 2

Alternative Agents for Ganciclovir Resistance or Intolerance

Foscarnet

• Foscarnet 60 mg/kg IV every 8 hours for 14-21 days is the recommended alternative when ganciclovir cannot be used 2, 1
• Foscarnet shows similar efficacy to ganciclovir but with different toxicity profile—primarily nephrotoxicity and electrolyte disturbances rather than myelosuppression 2, 4
• Administer foscarnet slowly over 2 hours (no faster than 1 mg/kg/minute) with saline fluid loading to minimize renal toxicity 2

Cidofovir

• Cidofovir is a third-line agent reserved for cases where both ganciclovir and foscarnet have failed or are contraindicated 1
• Cidofovir carries substantial nephrotoxicity risk and requires probenecid premedication plus aggressive IV hydration 2, 5
• Limited data support its use as primary therapy, and it should not be considered first-line 5

Treatment Duration and Monitoring

Duration Guidelines

• Continue treatment for minimum 14-21 days AND until CMV is no longer detectable in blood by PCR or antigenemia assay 2, 1
• For CMV retinitis, 21 days of induction is standard before transitioning to maintenance 2, 6

Monitoring Requirements

• Weekly CMV viral load by PCR is essential to assess treatment response 2, 1
• Monitor complete blood count twice weekly during induction phase due to high risk of neutropenia, anemia, and thrombocytopenia 2, 7
• Check serum creatinine, electrolytes (calcium, phosphorus, magnesium, potassium) twice weekly, especially with foscarnet therapy 2

Maintenance Therapy

CMV Retinitis

• After successful induction, maintenance therapy with valganciclovir 900 mg once daily is required lifelong in HIV-infected patients until immune reconstitution (CD4+ >100 cells/µL sustained for 3-6 months) 2, 6
• Alternative maintenance options include IV ganciclovir 5 mg/kg daily 5-7 days per week or intraocular ganciclovir implant plus oral valganciclovir 2

Other CMV Disease

• Maintenance therapy is generally not required for non-retinitis CMV disease if immune function can be restored 2, 1

Critical Adjunctive Measures

Immunosuppression Management

• Reduce or discontinue immunosuppressive medications whenever clinically feasible—this is associated with decreased mortality and improved clinical outcomes 2, 1
• In transplant recipients, balance reduction of immunosuppression against risk of rejection, monitoring graft function closely 2

HIV-Specific Considerations

• Initiate or optimize antiretroviral therapy (ART) concurrently with CMV treatment in all HIV-infected patients 1, 8
• Immune reconstitution is the ultimate goal to prevent CMV recurrence 2

Toxicity Management

Ganciclovir/Valganciclovir Toxicity

• Myelosuppression is the dose-limiting toxicity, occurring in up to 40% of patients 2
• Severe neutropenia (<500 cells/µL) or thrombocytopenia (<25,000/µL) requires dose reduction or temporary discontinuation 7
• Granulocyte colony-stimulating factor (G-CSF) can be used to manage neutropenia 2

Foscarnet Toxicity

• Nephrotoxicity occurs in up to 30% of patients—monitor creatinine closely and adjust doses for renal impairment 2
• Electrolyte abnormalities occur in approximately one-third of patients and can cause seizures or cardiac dysrhythmias 2
• Aggressive hydration and electrolyte monitoring/replacement are mandatory 2

Common Pitfalls to Avoid

• Never use oral valganciclovir as initial therapy for serious CMV disease—IV ganciclovir is required for adequate drug levels 2, 1
• Do not stop treatment based solely on symptom resolution—continue until viral clearance is documented by PCR 2, 1
• Do not overlook the need for ophthalmologic screening in HIV-infected patients with CD4+ <50 cells/µL, as CMV retinitis can be asymptomatic initially 2
• Avoid underdosing in patients with normal renal function—full doses are critical for treatment success 6, 7
• Do not forget that CMV viremia or positive cultures can represent asymptomatic shedding—tissue diagnosis with histopathology showing characteristic "owl's eye" inclusions is the gold standard for confirming invasive disease 2