Breakthrough CMV Infection Due to de Novo Letermovir Resistance in a Kidney Transplant Recipient: A Case Report

Cytomegalovirus (CMV) infection is one of the most significant complications after solid organ transplantation, particularly in high-risk D+/R- patients. Letermovir, a CMV terminase complex inhibitor, was approved by the FDA in 2017 for prophylaxis in CMV-seronegative hematopoietic stem cell transplant recipients. Its off-label use in solid organ transplant recipients has gained traction due to its favorable hematologic profile compared to valganciclovir. However, resistance development, particularly involving the UL56 V236M mutation, has been reported with the increased use of letermovir. Few articles discussed the clinical significance of letermovir resistance, especially in transplant recipients with breakthrough viremia. In this case report, we describe a rare de novo letermovir resistance in a kidney transplant patient, requiring a switch to valganciclovir.