Surveillance of CMV Terminase Gene Mutations in Allogeneic Hematopoietic Stem Cell Transplant Recipients Receiving Letermovir Prophylaxis
Abstract
Letermovir (LMV), a CMV-specific terminase inhibitor, is recommended for cytomegalovirus (CMV) prophylaxis in CMV-seropositive allogeneic hematopoietic stem cell transplant (alloHSCT) recipients. The association between low-level CMV DNAemia during prophylaxis and the emergence of mutations in CMV terminase complex genes remains unclear. We retrospectively analyzed 127 alloHSCT recipients at Saint-Louis Hospital, Paris, receiving LMV prophylaxis (108 primary, 24 secondary, and 5 both). Weekly CMV DNAemia monitoring was performed, and samples with viral loads ≥ 3 log IU/mL underwent whole-genome next-generation sequencing to detect mutations in terminase complex genes. During LMV prophylaxis, CMV DNAemia was detected in 31.5% of primary and 62.5% of secondary prophylaxis patients; however, viral loads ≥ 3 log IU/mL remained low in both groups (8.3%). The frequency of polymorphisms in terminase complex genes increased 2.5-fold during prophylaxis compared with pre-prophylaxis, and then decreased 3.0-fold after prophylaxis withdrawal. Confirmed LMV resistance was found in two patients, representing 1.6% of all patients and 18.2% of those with CMV DNAemia ≥ 3 log IU/mL. Two additional patients harbored mutations at resistance-associated positions in UL56 and UL89, totaling 36% of patients with viral loads ≥ 3 log IU/mL displaying mutations at known resistance sites. Clinically significant CMV infections were successfully managed with preemptive therapies. This study confirms the efficacy of LMV prophylaxis and demonstrates that LMV exerts selective pressure on the terminase complex, increasing the risk of resistance when CMV DNA levels exceed 3 log IU/mL, underscoring the importance of timely consideration of alternative antiviral therapies when CMV replication persists.
Related
- Incidence and Outcomes of Human Adenovirus Infection and Disease in a Multicenter Cohort of Pediatric Allogeneic Hematopoietic Cell Transplant Recipients
- Safety and immunogenicity of a first dose of SARS‐CoV‐2 mRNA vaccine in allogeneic hematopoietic stem‐cells recipients
- Graft-versus-host disease prophylaxis shapes T cell biology and immune reconstitution after hematopoietic cell transplant
- Changes in Tacrolimus and Everolimus Trough Concentrations and Dose Requirements After Initiation and Discontinuation of Letermovir Prophylaxis in Kidney Transplant Recipients: A Single-Center Retrospective Study
- Infectious complications in kidney transplant recipients across Africa: a scoping review of epidemiology, microbiology, and prophylaxis strategies
BibTeX
@article{caillault2026surveillance,
title = {{Surveillance of CMV Terminase Gene Mutations in Allogeneic Hematopoietic Stem Cell Transplant Recipients Receiving Letermovir Prophylaxis}},
author = {Amandine Caillault and Alienor Xhaard and Severine Mercier-Delarue and Linda Feghoul and Julien Robert and Nathalie Schnepf and David Michonneau and Marie Robin and Flore Sicre de Fontbrune and Eleonore Kaphan and Mathilde Ruggiu-Goiran and Pedro Henrique de Lima Prata and Florian Chevillon and Matthieu Jestin and Nathalie Dhedin and Gerard Socie and Régis Peffault de Latour and Maud Salmona and Jérôme Legoff},
journal = {Journal of Medical Virology},
year = {2026},
month = jul,
doi = {10.1002/jmv.71053},
url = {https://hal.science/hal-05782795v1},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Surveillance of CMV Terminase Gene Mutations in Allogeneic Hematopoietic Stem Cell Transplant Recipients Receiving Letermovir Prophylaxis
AU - Amandine Caillault
AU - Alienor Xhaard
AU - Severine Mercier-Delarue
AU - Linda Feghoul
AU - Julien Robert
AU - Nathalie Schnepf
AU - David Michonneau
AU - Marie Robin
AU - Flore Sicre de Fontbrune
AU - Eleonore Kaphan
AU - Mathilde Ruggiu-Goiran
AU - Pedro Henrique de Lima Prata
AU - Florian Chevillon
AU - Matthieu Jestin
AU - Nathalie Dhedin
AU - Gerard Socie
AU - Régis Peffault de Latour
AU - Maud Salmona
AU - Jérôme Legoff
PY - 2026
DA - 2026/07/10
JO - Journal of Medical Virology
DO - 10.1002/jmv.71053
UR - https://hal.science/hal-05782795v1
AB - Letermovir (LMV), a CMV-specific terminase inhibitor, is recommended for cytomegalovirus (CMV) prophylaxis in CMV-seropositive allogeneic hematopoietic stem cell transplant (alloHSCT) recipients. The association between low-level CMV DNAemia during prophylaxis and the emergence of mutations in CMV terminase complex genes remains unclear. We retrospectively analyzed 127 alloHSCT recipients at Saint-Louis Hospital, Paris, receiving LMV prophylaxis (108 primary, 24 secondary, and 5 both). Weekly CMV DNAemia monitoring was performed, and samples with viral loads ≥ 3 log IU/mL underwent whole-genome next-generation sequencing to detect mutations in terminase complex genes. During LMV prophylaxis, CMV DNAemia was detected in 31.5% of primary and 62.5% of secondary prophylaxis patients; however, viral loads ≥ 3 log IU/mL remained low in both groups (8.3%). The frequency of polymorphisms in terminase complex genes increased 2.5-fold during prophylaxis compared with pre-prophylaxis, and then decreased 3.0-fold after prophylaxis withdrawal. Confirmed LMV resistance was found in two patients, representing 1.6% of all patients and 18.2% of those with CMV DNAemia ≥ 3 log IU/mL. Two additional patients harbored mutations at resistance-associated positions in UL56 and UL89, totaling 36% of patients with viral loads ≥ 3 log IU/mL displaying mutations at known resistance sites. Clinically significant CMV infections were successfully managed with preemptive therapies. This study confirms the efficacy of LMV prophylaxis and demonstrates that LMV exerts selective pressure on the terminase complex, increasing the risk of resistance when CMV DNA levels exceed 3 log IU/mL, underscoring the importance of timely consideration of alternative antiviral therapies when CMV replication persists.
SN - 0146-6615
SN - 1096-9071
ER -