The emergence of letermovir and maribavir drug-resistant mutations: from clinical trials to real-world studies

Zhu, VZ; Horton, MB; Haeusler, GM; Yong, MK

Author(s): Zhu, VZ; Horton, MB; Haeusler, GM; Yong, MK;
Details: Publication Year 2024-12-01,Volume 37,Issue #6,Page 536-546
Journal Title: Current Opiniion in Infectious Diseases
Abstract: PURPOSE OF REVIEW: Cytomegalovirus (CMV) infection is associated with severe clinical disease and high morbidity in immunocompromised hosts. Letermovir and maribavir, are two recently developed antiviral drugs used in the prevention and treatment of resistant and refractory CMV. Following the publication of landmark randomized trials and increased use, both clinical trial data and real-world experience has reported the development of antiviral drug resistance. The aim of this review was to comprehensively review the published literature on letermovir and maribavir drug resistance and to describe the clinical scenarios in which they may emerge. RECENT FINDINGS: For letermovir, the most frequently detected resistance mutations occur in the UL56 gene (C325Y/W/F) and confer total resistance. Maribavir resistance mutations most often occur in the UL97 gene and resistance-associated variants (RAVs) T409M, H411Y, C480F have all been detected. The clinical context in which letermovir and maribavir resistance occurs include high viral loads at initiation, intensified immunosuppression, subtherapeutic drug exposure because of poor adherence, drug interactions, and inadequate central nervous system (CNS) penetration. Emergence of resistance mutations generally occurs within the first 3 months of initiation. SUMMARY: The detection of letermovir and maribavir resistance mutations highlights an ongoing clinical challenge in the management of CMV.
Publisher: LWW
Keywords: Humans; *Antiviral Agents/therapeutic use; *Drug Resistance, Viral/genetics; *Ribonucleosides/therapeutic use/pharmacology; *Cytomegalovirus Infections/drug therapy/virology; *Mutation; *Cytomegalovirus/genetics/drug effects; *Benzimidazoles/therapeutic use/pharmacology; *Quinazolines/therapeutic use; *Acetates/therapeutic use/pharmacology; Clinical Trials as Topic; Dichlororibofuranosylbenzimidazole/analogs & derivatives
Research Division(s): Immunology
PubMed ID: 39331647
Publisher's Version: https://doi.org/10.1097/qco.0000000000001065
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-12-05 11:13:24

Last Modified: 2024-12-05 11:14:13