What is the recommended management for Cytomegalovirus (CMV) post lung transplant?

CMV Management Post Lung Transplant

For lung transplant recipients, a strategy of CMV surveillance testing by PCR followed by preemptive therapy for positive results is recommended, with consideration of letermovir prophylaxis through day 100 post-transplant for high-risk patients. 1

Risk Assessment and Prophylaxis Strategy

• CMV infections are common in lung transplant recipients, with 50-60% of CMV-seropositive recipients experiencing reactivation and 10-30% developing CMV disease despite prophylaxis 1
• Risk factors for CMV disease include:
  • Donor CMV-seropositive/recipient-negative (D+/R-) status (highest risk) 1
  • Advanced recipient age 2
  • Single-lung transplant 2
  • Chronic obstructive pulmonary disease 2
  • Use of T-cell depleting agents or treatment for rejection 1

Prophylaxis Recommendations

• Primary prophylaxis options:
  • Valganciclovir 900 mg once daily (adjusted for renal function) for at least 3-6 months post-transplant 1, 2
  • Consider extended prophylaxis (12 months) for high-risk patients (D+/R-), which significantly reduces CMV infection, disease, and disease severity 3
  • Letermovir may be considered for CMV-seropositive recipients through day 100 post-transplant (note: letermovir lacks HSV/VZV coverage, so continue HSV/VZV prophylaxis) 1

Surveillance Recommendations

• Weekly quantitative CMV viral load monitoring by PCR for at least 3-6 months post-transplant 1
• Continue surveillance during periods of augmented immunosuppression (e.g., treatment for rejection) 1
• Consider extended surveillance for patients with chronic rejection or ongoing immunosuppression 1

Management of CMV Infection/Disease

Preemptive Therapy for Asymptomatic Viremia

• Upon detection of CMV viremia (defined as PCR positivity in ≥2 consecutive samples obtained 1 week apart): 1
  • First-line: Valganciclovir 900 mg orally twice daily (adjusted for renal function) 1
  • Alternative: Intravenous ganciclovir 5 mg/kg twice daily if concerns about absorption or severe disease 1
  • Continue treatment for at least 2 weeks and until CMV is no longer detectable 1

Treatment of CMV Disease

• For non-severe CMV disease:

  • Oral valganciclovir 900 mg twice daily (adjusted for renal function) 1
  • Continue until CMV is no longer detectable by PCR 1

• For severe or tissue-invasive CMV disease:

  • Intravenous ganciclovir 5 mg/kg twice daily 1
  • Consider reducing immunosuppressive medications in life-threatening disease 1
  • Monitor graft function closely during treatment 1

Management of Resistant CMV

• For ganciclovir-resistant CMV or when ganciclovir is not tolerated:
  • Foscarnet intravenously 1
  • Cidofovir intravenously (caution: substantial nephrotoxicity) 1
  • Maribavir for refractory infections (infectious disease consultation recommended) 1
  • Consider testing for drug resistance if breakthrough infection occurs 1

Monitoring During and After Treatment

• Weekly monitoring of CMV viral load during treatment 1

• Monitor for medication side effects:

  • Ganciclovir/valganciclovir: neutropenia, thrombocytopenia 1, 2
  • Foscarnet: nephrotoxicity, electrolyte abnormalities 1
  • Cidofovir: nephrotoxicity, ocular toxicity 1

• After successful treatment, resume surveillance as per protocol 1

Special Considerations

• Suboptimal prophylaxis: Valganciclovir at reduced doses (<900 mg/day) or for less than 6 months is associated with increased risk of CMV disease 2
• Late-onset CMV disease: Common after discontinuation of prophylaxis, particularly in D+/R- patients 4
• Extended prophylaxis benefits: 12 months of valganciclovir prophylaxis (vs. standard 3 months) reduces CMV disease from 32% to 4% in high-risk patients 3
• Breakthrough infections: May occur during prophylaxis (9% of cases) at a median of 6.7 months post-transplant 2

Pitfalls and Caveats

• Acyclovir and valacyclovir have excellent safety profiles but are only weakly active against CMV and are not recommended for CMV prophylaxis or treatment 1
• CMV-attributable mortality can be significant (5%), especially with ganciclovir-resistant disease 2
• Balancing prophylaxis duration against toxicity is crucial; extended prophylaxis increases efficacy but may increase adverse events 5
• Valganciclovir is associated with higher rates of leukopenia compared to oral ganciclovir (15.8% vs 2.3%) 5