Abstract: SA-PO1139
Breakthrough Cytomegalovirus (CMV) Infection Due to De Novo Letermovir Resistance in a Kidney Transplant Recipient
Session Information
- Transplantation: Clinical - Infectious Diseases
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2002 Transplantation: Clinical
Authors
- Weerasinghe, Sanjeeva Neranjan, Banner - University Medical Center Tucson, Tucson, Arizona, United States
- Hada, Muzammeel Dosanbhai, Banner - University Medical Center Tucson, Tucson, Arizona, United States
- Qannus, Abd Assalam, Banner - University Medical Center Tucson, Tucson, Arizona, United States
Introduction
Cytomegalovirus 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, is utilized 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. With its increased use, CMV has developed resistance using the UL56 genotype. In this case report, we describe a rare de novo letermovir resistance in a Kidney transplant patient.
Case Description
A 31-year-old female with end-stage kidney disease secondary to congenital Fanconi syndrome received a deceased donor kidney transplant in April 2024, complicated with delayed graft function. She was discharged on valganciclovir as prophylaxis for CMV. One month later, her regimen changed from valganciclovir to letermovir due to new leukopenia. She developed CMV viremia after one month on prophylaxis with letermovir despite remaining compliant with her regimen.Next generation sequencing detected the UL56 V236M mutation, which is known to confer resistance to letermovir. She was subsequently treated with ganciclovir.
Discussion
This case is an important example of a clinically significant CMV breakthrough infection due to de novo letermovir resistance. The patient's persistent viremia, despite adherence to prophylaxis, emphasizes the importance of maintaining high suspicion for resistance when viral loads fail to decline or increase unexpectedly. Any new, unexplained CMV viremia during prophylaxis should prompt resistance tests. It highlights that, while rare, resistance can happen and might be missed in clinical settings due to limited testing or delayed suspicion.To our knowledge, this is one of the few published cases describing clinically confirmed de novo UL56 V236M-mediated letermovir resistance in a kidney transplant recipient. It adds to the emerging recognition that resistance, while rare, can occur and may be underdiagnosed in clinical practice due to limited testing or delayed suspicion.
CMV Drug Resistance Profile
| Drug | Mutation Detected | Resistance Interpretation |
| Letermovir | UL 56 V236M | Resistant |
| Ganciclovir | None | Sensitive |
| Foscarnet | None | Sensitive |
| Cidofovir | None | Sensitive |