Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals.
Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals.
复制标题
DOI：
10.3390/v7122968
复制
发表时间：
2015-12-18
期刊：
影响因子：
--
通讯作者：
Felmlee DJ
中科院分区：
文献类型：
--
作者：
Ahmed A;Felmlee DJ
近年来，随着针对病毒编码的对病毒复制重要的蛋白NS3/4A、NS5A和NS5B的直接作用抗病毒药物的开发，慢性丙型肝炎的治疗有了显著的转变。这些药物在2期和3期临床试验中显示出超过90%的高持续病毒反应（SVR）率；然而，在现实生活中，这一比例略低。丙型肝炎病毒耐药变异出现在大多数由于在给定宿主内的丙型肝炎病毒耐药变异的选择和生长而未达到SVR的患者中。这些与耐药性相关的突变取决于所使用的直接作用抗病毒药物的类别，并因丙型肝炎病毒基因型和亚型而异。对这些突变的理解在选择和组合使用药物方面具有明确的临床意义。在这篇综述中，我们描述了目前可用的药物的作用机制，并总结了临床相关的耐药数据。
There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR) rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.