What is the recommended treatment for a patient with suspected or confirmed CMV (Cytomegalovirus) infection, particularly for those who are immunocompromised or symptomatic?

Treatment of CMV Infection

For immunocompromised patients with suspected or confirmed CMV infection, initiate intravenous ganciclovir 5 mg/kg twice daily immediately, then transition to oral valganciclovir 900 mg twice daily after 3-5 days for a total treatment duration of 2-3 weeks. 1

Initial Treatment Strategy

The choice of initial therapy depends on disease severity and site of infection:

Systemic CMV Disease (Colitis, Esophagitis, Pneumonitis)

• Begin IV ganciclovir 5 mg/kg twice daily as first-line therapy to achieve rapid therapeutic drug levels during the critical initial phase 1
• After 3-5 days of IV therapy, transition to oral valganciclovir 900 mg twice daily to complete the treatment course 1, 2
• Continue treatment for 21-28 days or until complete symptom resolution 3
• For severe symptoms or concerns about oral absorption, maintain IV ganciclovir for the full treatment duration 3

CMV Retinitis in AIDS Patients

• For sight-threatening lesions (adjacent to optic nerve or fovea): Intravitreous ganciclovir implant plus oral valganciclovir 900 mg twice daily for induction 3
• For small peripheral lesions: Oral valganciclovir 900 mg twice daily alone may be adequate 3
• Induction therapy: 900 mg twice daily for 21 days 4
• Maintenance therapy: 900 mg once daily indefinitely until immune recovery 4

CNS CMV Infection (Encephalitis, Ventriculitis)

• Combination therapy with IV ganciclovir plus IV foscarnet is preferred to maximize response and stabilize disease, despite higher adverse effect rates 3
• Prompt initiation is critical for optimal clinical response 3
• Consider delaying antiretroviral therapy (ART) initiation until clinical improvement occurs to avoid inflammatory complications 3

Treatment Duration and Monitoring

Continue antiviral therapy for at least 2-3 weeks and until CMV is no longer detected by PCR 3, 1:

• Monitor CMV viral load weekly by PCR to assess treatment response 3, 1
• Check complete blood counts twice weekly during induction and weekly during maintenance phase 1
• Monitor renal function and electrolytes twice weekly, especially if using foscarnet 1, 2

For CMV colitis specifically, treatment duration is 21-28 days or until complete symptom resolution 3.

Immunosuppression Management

Reduce or discontinue immunosuppressive therapy if clinically feasible while treating CMV syndrome 1:

• In transplant recipients, balance rejection risk against CMV disease severity 1
• In HIV-infected patients, initiate or optimize ART concurrently with CMV treatment 3, 1
• Continue ART until immune recovery occurs (CD4+ count >100 cells/µL sustained for 3-6 months) 1
• No data suggest that starting ART worsens CMV retinitis, gastrointestinal disease, or pneumonitis 3

Alternative Agents for Resistance or Intolerance

When ganciclovir/valganciclovir cannot be used:

Foscarnet (First Alternative)

• Dose: 90 mg/kg IV twice daily for established disease 1, 2
• Primary alternative for ganciclovir resistance or intolerance 1
• Requires strict monitoring of renal function and electrolytes due to significant nephrotoxicity risk 1
• Common adverse effects include nephrotoxicity, electrolyte abnormalities (hypocalcemia, hypomagnesemia), and neurologic dysfunction including seizures 1

Cidofovir (Third-Line)

• Reserved for refractory cases when both ganciclovir and foscarnet have failed or are contraindicated 1, 2
• Substantial nephrotoxicity risk limits its use 3, 1

Maribavir (Emerging Option)

• Shows promise for refractory or resistant CMV infections in clinical trials 5

Special Clinical Scenarios

Pediatric Patients

• For children with severe immunocompromise (e.g., SCID), maintain parenteral ganciclovir for the full 14-21 day course rather than switching to oral therapy, as early transition may promote CMV reactivation 2
• Limited data exists on appropriate valganciclovir dosing for children; for those old enough to receive adult dosing, valganciclovir is preferred over oral ganciclovir 5
• Immunocompromised children with encephalitis require IV acyclovir 10 mg/kg three times daily for at least 21 days 3

Surgical Considerations for CMV Colitis

• Emergency surgery is indicated only for: toxic megacolon, fulminant colitis, perforation, or ischemia 1, 2
• Obtain early surgical consultation on admission given extremely high mortality risk (approaching 70% even with treatment) 2
• Use damage control approach in severely ill patients 1

Transplant Recipients

• For prevention in high-risk solid organ transplant recipients (D+/R-): valganciclovir 900 mg once daily starting within 10 days of transplantation 4
• Duration: 100 days for heart/kidney-pancreas transplants, 200 days for kidney transplants 4
• Letermovir may be considered as primary prophylaxis for CMV-seropositive allogeneic hematopoietic stem cell transplant recipients 3

Critical Pitfalls to Avoid

Do not delay treatment while awaiting biopsy results if clinical suspicion is high, particularly in severe disease or neurological involvement 1:

• Untreated CMV disease in immunodeficient patients carries 70% mortality in severely ill patients 1
• Begin ganciclovir immediately when CMV infection is suspected clinically 1, 2

Do not rely on blood serology for diagnosis in acute CMV syndrome, as 70% of adults are CMV seropositive at baseline 1:

• Confirm diagnosis with tissue biopsy showing CMV-specific immunohistochemistry and characteristic "owl's eye" intranuclear inclusions 1
• Positive CMV culture or PCR alone without histopathological confirmation is insufficient, as subclinical reactivation is common and may be self-limiting 1

Do not use acyclovir or valacyclovir for CMV treatment, as they have excellent safety profiles but are only weakly active against CMV 3.

Expected Adverse Effects

Ganciclovir/Valganciclovir

• Myelosuppression is the major adverse effect: neutropenia, anemia, thrombocytopenia 1, 5, 4
• Dose reduction or interruption required in up to 40% of patients due to hematologic toxicity 1, 5
• Renal dysfunction may occur, requiring dose adjustment 5, 4
• Severe leukopenia, pancytopenia, bone marrow aplasia, and aplastic anemia have been reported 4

Foscarnet

• Nephrotoxicity and electrolyte abnormalities (hypocalcemia, hypomagnesemia, hypokalemia) 3, 1
• Neurologic dysfunction including seizures 1
• Better tolerated than cidofovir despite toxicity profile 3

Cidofovir

• Substantial nephrotoxicity 3, 1
• Ocular toxicity (less frequent) 3

Ophthalmologic Monitoring for CMV Retinitis

Indirect ophthalmoscopy through dilated pupil should be performed 3:

• At time of diagnosis
• After completion of induction therapy
• One month after initiation of therapy
• Monthly thereafter while on anti-CMV treatment 3
• Every 3 months after immune recovery 3

Monthly fundus photographs using standardized technique provide optimal method for following patients and detecting early relapse 3.