What is the recommended treatment approach for a pediatric patient with acquired Cytomegalovirus (CMV) infection, particularly in immunocompromised children?

Treatment of Acquired CMV in Immunocompromised Children

For immunocompromised pediatric patients with acquired CMV disease, treatment requires induction therapy with ganciclovir or valganciclovir followed by lifelong chronic maintenance therapy, as CMV disease is not cured with currently available antiviral agents. 1, 2

Initial Treatment Approach

Induction Therapy for Active CMV Disease

• High-dose induction therapy is mandatory using ganciclovir (5 mg/kg IV every 12 hours) or valganciclovir (oral equivalent dosing) for 14-21 days 2, 3, 4
• The choice between IV ganciclovir and oral valganciclovir depends on disease severity, ability to tolerate oral medications, and gastrointestinal absorption 3, 5
• For CMV retinitis specifically, induction consists of 900 mg valganciclovir twice daily for 21 days in adults; pediatric dosing is calculated based on body surface area and creatinine clearance 3

Maintenance Therapy (Secondary Prophylaxis)

• Lifelong chronic maintenance therapy is required following induction, as CMV disease recurs routinely without suppressive therapy 1, 2
• Effective maintenance regimens include:
  • Oral valganciclovir (preferred for convenience) 2, 3
  • Parenteral ganciclovir 1, 2
  • Parenteral foscarnet 1, 2
  • Combined parenteral ganciclovir and foscarnet 1, 2
  • Parenteral cidofovir 1, 2
  • For retinitis only: ganciclovir intraocular implant plus oral ganciclovir 1, 2

Pediatric-Specific Considerations

Dosing Calculations

• Pediatric valganciclovir dosing is calculated using the formula: Dose (mg) = 7 × BSA × CrCl (using modified Schwartz formula) 3
• Maximum creatinine clearance value of 150 mL/min/1.73m² should be used if calculated value exceeds this 3
• K values for Schwartz formula vary by age: 0.33 for low birth weight infants <1 year, 0.45 for appropriate birth weight infants <1 year and children 1-2 years, 0.55 for boys 2-13 years and girls 2-16 years 3

Monitoring Requirements

• HIV-infected children who are CMV-infected and severely immunosuppressed should undergo dilated retinal examination by an ophthalmologist every 4-6 months 1
• Older children should be counseled to recognize visual symptoms including "floaters" 1
• Complete blood counts, platelet counts, and creatinine levels must be monitored frequently during treatment due to hematologic toxicity risk 3

Prevention Strategies in Immunocompromised Children

Primary Prophylaxis

• Oral ganciclovir or valganciclovir may be considered for severely immunosuppressed CMV-infected children (e.g., CD4+ count <50 cells/µL in HIV-infected patients) 1
• However, routine prophylaxis is generally not recommended due to neutropenia, anemia, conflicting efficacy data, lack of survival benefit, risk of ganciclovir-resistant CMV, and cost 1, 2
• The most important prevention method is early recognition of disease manifestations through patient/caregiver education and regular monitoring 1

Screening Recommendations

• Obtain CMV urine culture on all HIV-infected or exposed infants at birth or early postnatal visit to identify congenital CMV infection 1
• Beginning at age 1 year, perform annual CMV antibody testing for CMV-seronegative, severely immunosuppressed HIV-infected children to identify those who acquire CMV and may benefit from retinitis screening 1

Exposure Prevention

• CMV-seronegative children requiring blood transfusion should receive only CMV antibody-negative or leukocyte-reduced cellular blood products in non-emergency situations 1
• Parents and caregivers should be informed that children in daycare facilities are at increased risk for CMV acquisition 1
• Risk reduction requires optimal hygiene practices including hand-washing and use of latex gloves 1

Solid Organ Transplant Recipients

Prophylaxis Protocol

• High-risk pediatric transplant recipients (D+/R-) should receive valganciclovir prophylaxis starting within 10 days of transplantation 3, 6
• Duration varies by organ: 100 days for heart transplant, 200 days for kidney transplant 3
• Standardized protocols improve appropriate prophylaxis provision and reduce CMV disease occurrence 7

Hybrid Strategy

• A hybrid approach bridging prophylaxis and pre-emptive therapy is emerging as an additional prevention method 6
• Routine surveillance with quantitative PCR enables early detection and treatment of asymptomatic CMV DNAemia 4, 7

Critical Toxicity Monitoring

Hematologic Toxicity

• Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow aplasia, and aplastic anemia can occur 3
• Dose modification or discontinuation may be required based on laboratory values 3
• Neutropenia is common but associated with few invasive infections when appropriately monitored 7

Drug Resistance

• Extended ganciclovir use increases risk of developing drug-resistant CMV 2
• Foscarnet is the alternative for ganciclovir-resistant CMV 2
• Cidofovir may be considered as third-line therapy 2

Discontinuation of Maintenance Therapy (HIV-Infected Patients Only)

• Maintenance therapy may be discontinued in patients with CMV retinitis when CD4+ count increases to >100-150 cells/µL, sustained for >3-6 months on antiretroviral therapy, with suppressed HIV viral load 1, 2
• This decision should be made in consultation with an ophthalmologist, considering magnitude and duration of CD4+ increase, viral load suppression, anatomic location of retinal lesions, vision in contralateral eye, and feasibility of regular monitoring 1
• Restart prophylaxis when CD4+ count decreases to <50-100 cells/µL 1

Important Caveats

Contraindications

• Acyclovir is not effective for CMV disease prevention and should not be used 1
• Valacyclovir is contraindicated for CMV prophylaxis due to unexplained increased mortality in AIDS patients 1, 8

Fertility and Carcinogenicity Warnings

• Valganciclovir may cause temporary or permanent inhibition of spermatogenesis based on animal data 3
• The drug has potential to cause birth defects and cancers in humans based on animal studies 3
• Males should practice barrier contraception during and for at least 90 days following treatment 3

Transplant-Specific Outcomes

• Development of CMV viremia following ganciclovir prophylaxis is associated with significantly decreased 1-year survival and increased non-relapse mortality in pediatric allogeneic stem cell transplant recipients 9
• This finding emphasizes the critical importance of preventing CMV viremia through appropriate prophylaxis strategies 9