Genetic Variants Associated with Drug Resistance of Cytomegalovirus in Hematopoietic Cell Transplantation Recipients

• Published in: Viruses Vol. 15; no. 6; p. 1286
• Main Authors: Chae, Seungwan, Kim, Hoon Seok, Cho, Sung-Yeon, Nho, Dukhee, Lee, Raeseok, Lee, Dong-Gun, Kim, Myungshin, Kim, Yonggoo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30-05-2023; MDPI
• Subjects: Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Cytomegalovirus; Cytomegalovirus - genetics; Cytomegalovirus Infections; Cytomegaloviruses; Disease prevention; Drug resistance; Drug Resistance, Viral - genetics; Drug therapy; Genes; Genetic aspects; Genetic diversity; Genetic testing; Graft versus host disease; Graft-versus-host reaction; Hematology; hematopoietic cell transplantation; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic stem cells; Humans; Infections; Kinases; Leukemia; Medical research; Medicine, Experimental; Mortality; Patients; pharmacogenomic variants; Software; Stem cell transplantation; Transplant Recipients; Transplantation; Transplants & implants; UL97; Variance analysis; viral; South Korea; United States > US; Germany; UL54; pharmacogenomic variants; UL97; cytomegalovirus; hematopoietic cell transplantation; viral; drug resistance
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v15061286

Cytomegalovirus (CMV) infection is a serious complication in hematopoietic cell transplantation (HCT) recipients. Drug-resistant strains make it more challenging to treat CMV infection. This study aimed to identify variants associated with CMV drug resistance in HCT recipients and assess their clinical significance. A total of 123 patients with refractory CMV DNAemia out of 2271 HCT patients at the Catholic Hematology Hospital between April 2016 and November 2021 were analyzed, which accounted for 8.6% of the 1428 patients who received pre-emptive therapy. Real-time PCR was used to monitor CMV infection. Direct sequencing was performed to identify drug-resistant variants in
and
. Resistance variants were found in 10 (8.1%) patients, and variants of uncertain significance (VUS) were found in 48 (39.0%) patients. Patients with resistance variants had a significantly higher peak CMV viral load than those without (
= 0.015). Patients with any variants had a higher risk of severe graft-versus-host disease and lower one-year survival rates than those without (
= 0.003 and
= 0.044, respectively). Interestingly, the presence of variants reduced the rate of CMV clearance, particularly in patients who did not modify their initial antiviral regimen. However, it had no apparent impact on individuals whose antiviral regimens were changed due to refractoriness. This study highlights the importance of identifying genetic variants associated with CMV drug resistance in HCT recipients for providing appropriate antiviral treatment and predicting patient outcomes.