Violet Z Zhu, Miles B Horton, Gabrielle M Haeusler, Michelle K Yong
{"title":"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。","authors":"Violet Z Zhu, Miles B Horton, Gabrielle M Haeusler, Michelle K Yong","doi":"10.1097/QCO.0000000000001065","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of review: </strong>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.</p><p><strong>Recent findings: </strong>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.</p><p><strong>Summary: </strong>The detection of letermovir and maribavir resistance mutations highlights an ongoing clinical challenge in the management of CMV.</p>","PeriodicalId":10880,"journal":{"name":"Current Opinion in Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The emergence of letermovir and maribavir drug-resistant mutations: from clinical trials to real-world studies.\",\"authors\":\"Violet Z Zhu, Miles B Horton, Gabrielle M Haeusler, Michelle K Yong\",\"doi\":\"10.1097/QCO.0000000000001065\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose of review: </strong>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.</p><p><strong>Recent findings: </strong>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.</p><p><strong>Summary: </strong>The detection of letermovir and maribavir resistance mutations highlights an ongoing clinical challenge in the management of CMV.</p>\",\"PeriodicalId\":10880,\"journal\":{\"name\":\"Current Opinion in Infectious Diseases\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current Opinion in Infectious Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/QCO.0000000000001065\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/27 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Opinion in Infectious Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/QCO.0000000000001065","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/27 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
The emergence of letermovir and maribavir drug-resistant mutations: from clinical trials to real-world studies.
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.
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.