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

IF 3.6 3区 医学 Q2 INFECTIOUS DISEASES
Current Opinion in Infectious Diseases Pub Date : 2024-12-01 Epub Date: 2024-09-27 DOI:10.1097/QCO.0000000000001065
Violet Z Zhu, Miles B Horton, Gabrielle M Haeusler, Michelle K Yong
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引用次数: 0

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.

来替莫韦和马立巴韦耐药性突变的出现:从临床试验到实际研究。
综述目的:巨细胞病毒(CMV)感染与免疫功能低下宿主的严重临床疾病和高发病率有关。来替莫韦和马立巴韦是最近开发的两种抗病毒药物,用于预防和治疗耐药和难治性 CMV。随着具有里程碑意义的随机试验的公布和使用的增加,临床试验数据和实际经验都报告了抗病毒药物耐药性的产生。本综述旨在全面回顾已发表的关于来特莫韦和马拉巴韦耐药性的文献,并描述可能出现耐药性的临床情况:对于来曲莫韦,最常检测到的耐药性突变发生在 UL56 基因(C325Y/W/F)中,并产生完全耐药性。马立巴韦的耐药性变异最常发生在 UL97 基因中,耐药性相关变异(RAV)T409M、H411Y、C480F 均已检测到。来替莫韦和马立巴韦耐药性产生的临床背景包括:起始时病毒载量高、免疫抑制加强、因依从性差而暴露于治疗以下药物、药物相互作用以及中枢神经系统(CNS)渗透不足。耐药突变一般发生在用药后的头 3 个月内。总结:发现来曲莫韦和马立巴韦耐药突变突显了 CMV 临床治疗中的一个持续挑战。
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来源期刊
CiteScore
6.70
自引率
2.60%
发文量
121
审稿时长
6-12 weeks
期刊介绍: This reader-friendly, bimonthly resource provides a powerful, broad-based perspective on the most important advances from throughout the world literature. Featuring renowned guest editors and focusing exclusively on two topics, every issue of Current Opinion in Infectious Disease delivers unvarnished, expert assessments of developments from the previous year. Insightful editorials and on-the-mark invited reviews cover key subjects such as HIV infection and AIDS; skin and soft tissue infections; respiratory infections; paediatric and neonatal infections; gastrointestinal infections; tropical and travel-associated diseases; and antimicrobial agents.
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