How is Cytomegalovirus (CMV) managed?

Management of Cytomegalovirus (CMV) Infection

Ganciclovir is the first-line therapy for CMV infections, typically administered intravenously at 5 mg/kg twice daily for 2-3 weeks, with an option to switch to oral valganciclovir after 3-5 days based on clinical response. 1, 2

Diagnostic Approach

• CMV detection methods:

  • PCR testing of blood for viral load (most common monitoring method)
  • Histopathology with immunohistochemistry (IHC) for tissue diagnosis (92-100% specificity)
  • CMV antigenaemia assays (semiquantitative)
  • Viral culture (highly specific but less sensitive)

• When to test:

  • Routine screening not indicated in general population
  • Weekly monitoring recommended for high-risk patients (transplant recipients, immunosuppressed)
  • Testing indicated in steroid-resistant inflammatory bowel disease 1

Treatment Protocols

Primary Treatment Options

1. Intravenous Ganciclovir:

   • Dosage: 5 mg/kg IV twice daily
   • Duration: 2-3 weeks or until CMV is no longer detected
   • Monitoring: Complete blood counts, electrolytes, renal function twice weekly 1, 2

2. Oral Valganciclovir:

   • Dosage: 900 mg twice daily (with food)
   • Can be used after initial IV ganciclovir therapy
   • Equivalent systemic exposure to IV ganciclovir when properly dosed 3, 4
   • Requires dose adjustment for renal impairment

3. Sequential Therapy Approach:

   • Initial IV ganciclovir (5 mg/kg twice daily for 3-5 days)
   • Followed by oral valganciclovir (900 mg twice daily)
   • Total treatment duration: 2-3 weeks 2, 4

Alternative Agents (for resistance or intolerance)

1. Foscarnet:

   • Dosage: 60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours
   • Used when ganciclovir resistance or intolerance occurs
   • Requires close monitoring for nephrotoxicity and electrolyte abnormalities 1

2. Combination Therapy:

   • Ganciclovir plus foscarnet recommended for severe cases (e.g., CMV encephalitis)
   • Has shown 74% improvement/stabilization in HIV patients with CNS disease 1

3. Cidofovir:

   • Reserved for cases resistant to both ganciclovir and foscarnet
   • Significant nephrotoxicity risk 1

Special Patient Populations

Transplant Recipients

• Allogeneic HCT recipients:

  • Weekly CMV viral load monitoring for preemptive therapy
  • Consider letermovir as primary prophylaxis for CMV-seropositive recipients
  • Surveillance period: 3-6 months post-transplant 1

• Solid Organ Transplant:

  • Preemptive therapy based on viral load monitoring
  • Treatment duration: minimum 2 weeks and until CMV is undetectable 5

Inflammatory Bowel Disease

• For steroid-resistant IBD with CMV:
  • Ganciclovir (5 mg/kg IV twice daily for 2-3 weeks)
  • Consider discontinuing immunosuppressants in severe cases 1, 2
  • For localized CMV colitis, most immunosuppressants can be maintained except thiopurines 2

Congenital CMV

• Treatment regimen:
  • Ganciclovir (6 mg/kg IV every 12 hours for 15-21 days)
  • Followed by valganciclovir (15 mg/kg every 12 hours for 6 weeks)
  • Consider measuring ganciclovir AUC in treatment failure 1

Monitoring During Treatment

1. Laboratory monitoring:

   • Complete blood counts twice weekly during induction, weekly thereafter
   • Serum electrolytes and renal function tests
   • CMV viral load to assess response 1, 2

2. Clinical monitoring:

   • Assess for resolution of symptoms
   • Monitor for drug toxicities (neutropenia, thrombocytopenia, renal dysfunction)
   • Consider repeat diagnostic testing in non-responsive cases 2

Management of Resistance

• When to suspect resistance:

  • Persistent or increasing viral load despite 2 weeks of appropriate therapy
  • Progressive clinical disease despite adequate treatment 2

• Management options:

  • Switch to foscarnet as first option
  • Consider cidofovir as second option
  • For severe cases, combination therapy with ganciclovir and foscarnet 2
  • Infectious disease consultation recommended 2

Common Pitfalls and Caveats

1. Drug toxicities:

   • Ganciclovir/valganciclovir: bone marrow suppression (neutropenia)
   • Foscarnet: nephrotoxicity and electrolyte disturbances
   • Cidofovir: substantial nephrotoxicity and potential ocular toxicity 1

2. Treatment duration:

   • Premature discontinuation can lead to relapse
   • Minimum 2 weeks and until CMV is undetectable 1, 2

3. Maintenance therapy:

   • Consider for high-risk patients (e.g., HIV with CMV retinitis)
   • Balance benefits against toxicity of long-term antiviral use 1

4. Drug interactions:

   • Dose adjustment needed when valganciclovir is coadministered with certain immunosuppressants
   • Letermovir lacks HSV/VZV coverage; continue HSV/VZV prophylaxis when using letermovir 1