Liver Unit, Internal Medicine Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain; Centro de Biología Molecular 'Severo Ochoa' (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, Madrid, Spain.
Int J Antimicrob Agents. 2020 Jul;56(1):105562. doi: 10.1016/j.ijantimicag.2018.10.005. Epub 2018 Oct 10.
Hepatitis C virus (HCV) follows quasispecies dynamics in infected hosts and this influences its biology, how the virus diversifies into several genotypes and many subtypes, and how viral populations respond to antiviral therapies. Despite current antiviral combinations being able to cure a great percentage of HCV-infected patients, the presence of resistance-associated substitutions (RASs) diminishes the success of antiviral therapies, which is a main concern in the re-treatment of patients treated with direct-acting antiviral agents. Current methodologies such as ultra deep sequencing are ideal tools to obtain a detailed representation of the mutant spectrum composition circulating in infected patients. Such knowledge should allow optimisation of rescue treatments. A new mechanism of antiviral resistance not based on the selection of RASs but on high viral fitness is discussed.
丙型肝炎病毒（HCV）在受感染的宿主中遵循准种动态，这影响了其生物学特性，包括病毒如何多样化成几种基因型和许多亚型，以及病毒群体如何对抗病毒治疗产生反应。尽管目前的抗病毒联合疗法能够治愈很大比例的 HCV 感染患者，但耐药相关突变（RAS）的存在降低了抗病毒治疗的成功率，这是重新治疗接受直接作用抗病毒药物治疗的患者的主要关注点。目前的方法，如超高深度测序，是获得受感染患者循环中突变谱组成的详细代表性的理想工具。这些知识应该可以优化挽救治疗。本文讨论了一种新的抗病毒耐药机制，该机制不基于 RAS 的选择，而是基于高病毒适应性。
