Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
Residency program in Microbiology and Virology, Università degli Studi di Milano. Milan, Italy.
Drug Resist Updat. 2018 Mar;37:17-39. doi: 10.1016/j.drup.2018.01.004. Epub 2018 Feb 21.
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.
如今，由于具有针对 NS3、NS5A 和 NS5B 病毒蛋白的强效直接作用抗病毒药物（DAA）的发展，有几种新的、非常有效的治疗慢性丙型肝炎病毒（HCV）感染的选择。耐药相关替代（RAS）的自然存在，以及它们在不完全药物压力下的快速出现，是 HCV 的固有特征，极大地影响了治疗效果和实现病毒学治愈的机会。迄今为止，大量的 NS3、NS5A 和 NS5B 中的 RAS 已在体内和/或体外与对 DAA 的敏感性降低相关，但尚无综合的 RAS 列表。因此，本综述提供了对目前批准的 DAA 或处于临床开发 II/III 期的针对 HCV 感染的 DAA 的 RAS 作用的最新、系统的概述，区分了它们在不同 HCV 基因型和 DAA 中的影响，为 HCV 耐药性检测在临床实践中的有效使用提供了帮助。
