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Hepatitis C virus drug resistance associated substitutions and their clinical relevance: Update 2018
Drug Resistance Updates ( IF 24.3 ) Pub Date : 2018-02-21 , DOI: 10.1016/j.drup.2018.01.004
Maria C Sorbo 1 , Valeria Cento 2 , Velia C Di Maio 1 , Anita Y M Howe 3 , Federico Garcia 4 , Carlo F Perno 5 , Francesca Ceccherini-Silberstein 1
Affiliation  

Nowadays, due to the development of potent Direct-Acting Antiviral Agents (DAAs) that specifically target NS3, NS5A and NS5B viral proteins, several new and highly efficacious options to treat chronic Hepatitis C virus (HCV) infection are available. The natural presence of resistance associated substitutions (RASs), as well as their rapid emergence during incomplete drug-pressure, are intrinsic characteristics of HCV that greatly affect treatment outcome and the chances to achieve a virolgical cure. To date, a high number of RASs in NS3, NS5A, and NS5B have been associated in vivo and/or in vitro with reduced susceptibility to DAAs, but no comprehensive RASs list is available. This review thus provides an updated, systematic overview of the role of RASs to currently approved DAAs or in phase II/III of clinical development against HCV-infection, discriminating their impact in different HCV-genotypes and DAAs, providing assistance for a fruitful use of HCV resistance testing in clinical practice.



中文翻译:

丙型肝炎病毒耐药性相关替代及其临床相关性:2018 年更新

如今,由于专门针对 NS3、NS5A 和 NS5B 病毒蛋白的强效直接作用抗病毒剂 (DAA) 的开发,有几种新的和高效的治疗慢性丙型肝炎病毒 (HCV) 感染的选择。耐药相关替代物 (RAS) 的自然存在,以及它们在不完全药物压力期间的快速出现,是 HCV 的内在特征,极大地影响了治疗结果和实现病毒学治愈的机会。迄今为止,NS3、NS5A 和 NS5B 中的大量 RAS 已在体内和/或体外相关联对 DAA 的敏感性降低,但没有全面的 RAS 列表可用。因此,本综述对 RAS 对目前批准的 DAA 或在抗 HCV 感染的临床开发 II/III 期中的作用提供了更新的、系统的概述,区分了它们对不同 HCV 基因型和 DAA 的影响,为有效使用临床实践中的 HCV 耐药性检测。

更新日期:2018-02-21
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