Dual Resistance to Maribavir and Ganciclovir in Transplant Recipients

Background: Human cytomegalovirus (CMV) remains an important pathogen, especially for immunocompromised patients such as solid organ and hematopoietic stem cell recipients. Viral genomic mutations conferring drug resistance are an important impediment to effective CMV management and frequently lead...

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Main Author: Steven B. Kleiboeker
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/17/3/421
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author Steven B. Kleiboeker
author_facet Steven B. Kleiboeker
author_sort Steven B. Kleiboeker
collection DOAJ
description Background: Human cytomegalovirus (CMV) remains an important pathogen, especially for immunocompromised patients such as solid organ and hematopoietic stem cell recipients. Viral genomic mutations conferring drug resistance are an important impediment to effective CMV management and frequently lead to use of alternative antiviral drugs to treat CMV disease. Methods: Results from 1459 de-identified patient samples with both UL54 and UL97 sequencing results were analyzed for ganciclovir (GCV) and maribavir (MBV) resistance mutations. Genomic sequencing was performed by the Sanger method and resistance mutations were identified by comparison to CMV reference strain AD169. Results: Ganciclovir resistance was identified in 379 of 1459 (25.98%) of the samples tested, with most resistance-conferring mutations present in viral gene UL97. A total of 121 of 1459 (8.29%) samples had MBV resistance mutations, and 84 (69.42%) of the 121 samples with MBV resistance also had GCV resistance mutations. Of the 84 samples with resistance to both MBV and GCV, 35 (41.67%) had a single UL97 mutation conferring resistance to both drugs, either C480F or F342Y. The overall prevalence of C480F was increased relative to an earlier analysis of samples from this reference laboratory. Conclusions: Although a high prevalence of CMV resistance mutations was identified, this must be taken in the context of healthcare providers submitting samples from patients with suspected CMV resistance. Most MBV-resistant samples were also resistant to GCV, suggesting that use of MBV as an alternative to GCV may benefit from genotypic resistance testing to achieve the effective control of CMV disease.
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spelling doaj-art-412a39da77df413b89ffb87f3dd6bcdf2025-08-20T01:50:10ZengMDPI AGViruses1999-49152025-03-0117342110.3390/v17030421Dual Resistance to Maribavir and Ganciclovir in Transplant RecipientsSteven B. Kleiboeker0Eurofins Viracor Clinical Diagnostics, 18000 West 99th Street, Lenexa, KS 66219, USABackground: Human cytomegalovirus (CMV) remains an important pathogen, especially for immunocompromised patients such as solid organ and hematopoietic stem cell recipients. Viral genomic mutations conferring drug resistance are an important impediment to effective CMV management and frequently lead to use of alternative antiviral drugs to treat CMV disease. Methods: Results from 1459 de-identified patient samples with both UL54 and UL97 sequencing results were analyzed for ganciclovir (GCV) and maribavir (MBV) resistance mutations. Genomic sequencing was performed by the Sanger method and resistance mutations were identified by comparison to CMV reference strain AD169. Results: Ganciclovir resistance was identified in 379 of 1459 (25.98%) of the samples tested, with most resistance-conferring mutations present in viral gene UL97. A total of 121 of 1459 (8.29%) samples had MBV resistance mutations, and 84 (69.42%) of the 121 samples with MBV resistance also had GCV resistance mutations. Of the 84 samples with resistance to both MBV and GCV, 35 (41.67%) had a single UL97 mutation conferring resistance to both drugs, either C480F or F342Y. The overall prevalence of C480F was increased relative to an earlier analysis of samples from this reference laboratory. Conclusions: Although a high prevalence of CMV resistance mutations was identified, this must be taken in the context of healthcare providers submitting samples from patients with suspected CMV resistance. Most MBV-resistant samples were also resistant to GCV, suggesting that use of MBV as an alternative to GCV may benefit from genotypic resistance testing to achieve the effective control of CMV disease.https://www.mdpi.com/1999-4915/17/3/421cytomegalovirusresistancemaribavirganciclovir
spellingShingle Steven B. Kleiboeker
Dual Resistance to Maribavir and Ganciclovir in Transplant Recipients
Viruses
cytomegalovirus
resistance
maribavir
ganciclovir
title Dual Resistance to Maribavir and Ganciclovir in Transplant Recipients
title_full Dual Resistance to Maribavir and Ganciclovir in Transplant Recipients
title_fullStr Dual Resistance to Maribavir and Ganciclovir in Transplant Recipients
title_full_unstemmed Dual Resistance to Maribavir and Ganciclovir in Transplant Recipients
title_short Dual Resistance to Maribavir and Ganciclovir in Transplant Recipients
title_sort dual resistance to maribavir and ganciclovir in transplant recipients
topic cytomegalovirus
resistance
maribavir
ganciclovir
url https://www.mdpi.com/1999-4915/17/3/421
work_keys_str_mv AT stevenbkleiboeker dualresistancetomaribavirandganciclovirintransplantrecipients