Comparative emergence of maribavir and ganciclovir resistance in a randomized phase 3 clinical trial for treatment of cytomegalovirus infection Journal Article


Authors: Chou, S.; Winston, D. J.; Avery, R. K.; Cordonnier, C.; Duarte, R. F.; Haider, S.; Maertens, J.; Peggs, K. S.; Solano, C.; Young, J. A. H.; Gu, J.; Pocock, G.; Papanicolaou, G. A.
Article Title: Comparative emergence of maribavir and ganciclovir resistance in a randomized phase 3 clinical trial for treatment of cytomegalovirus infection
Abstract: Background. Among 547 patients receiving maribavir or valganciclovir for first-episode cytomegalovirus infection after hematopoietic cell transplant, the treatment response rate was 69.6% and 77.4% respectively. Development of maribavir and ganciclovir resistance was compared after receiving either drug. Methods. Viral mutations conferring drug resistance were analyzed in plasma DNA extracts at baseline and posttreatment. Results. Prior antiviral drug exposure was limited, with only 2 instances of baseline drug resistance detected. An equal number (n = 241) received valganciclovir or maribavir for at least 21 days (median, 55–56 days). Among them, drug resistance mutations were detected in 24 (10%) maribavir recipients at 35–125 days (median, 56 days) after starting therapy, including in 12 of 14 who experienced a viral load rebound while on therapy. Ganciclovir resistance mutations developed in 6 (2.5%) valganciclovir recipients at 66–110 days (median, 90 days). One maribavir recipient developed a novel UL97 gene mutation (P-loop substitution G343A) that conferred strong maribavir and ganciclovir resistance in vitro. Viral clearance was confirmed in 17 (74%) of 23 patients with emergent maribavir resistance after retreatment with an alternative CMV antiviral drug. Conclusions. After 3–8 weeks of therapy, maribavir resistance emerged earlier and more frequently than ganciclovir resistance but was usually treatable using alternative therapy. © The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
Keywords: cytomegalovirus; antiviral therapy; valganciclovir; maribavir; antiviral drug resistance
Journal Title: Journal of Infectious Diseases
Volume: 231
Issue: 3
ISSN: 0022-1899
Publisher: Oxford University Press  
Date Published: 2025-03-15
Start Page: e470
End Page: e477
Language: English
DOI: 10.1093/infdis/jiae469
PUBMED: 39302855
PROVIDER: scopus
PMCID: PMC11911792
DOI/URL:
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus
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