Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal.
Laboratory of Viral Hepatitis, National Center for Microbiology, Institute of Health Carlos III, Carretera Majadahonda-Pozuelo km 2.2, Majadahonda, 28220, Madrid, Spain.
Sci Rep. 2020 Aug 3;10(1):13024. doi: 10.1038/s41598-020-69692-7.
Hepatitis C virus (HCV) infection remains a global health problem. Previously, the prevalence of NS5A resistance-associated substitutions (RASs) to elbasvir, a new direct-acting antiviral (DAA) against the NS5A viral protein was assessed by our group before its introduction into clinical use in Spain. However, the origin, epidemic history, transmission dynamics, diversity and baseline RASs to NS5A direct-acting agents of HCV-GT1a in Spain remain unknown. A nationwide cross-sectional survey of individuals chronically-infected with HCV-G1a and DAAs-naïve was performed. HCV population sequencing, phylogenetic analysis and Bayesian methods were used. GT1a clade II was more prevalent than clade I (82.3% vs. 17.7%; P < 0.001) and older (estimated origin in 1912 vs. 1952). Clade II epidemic is currently declining whereas clade I epidemic has reached equilibrium. A total of 58 single RASs were identified, which account for the moderate level (10%) of baseline resistance observed. When considering the regional data, marked differences were observed, with thirteen regions showing an intermediate level (5-15%) and one a high level (20%) of resistance. Current HCV-GT1a epidemic in Spain is driven by clade I which seem to have different dissemination routes relative to clade II. A moderate level of baseline RASs to NS5A-DAAs with marked differences among regions was observed. Close surveillance of response to treatment with DAAs will be important.
丙型肝炎病毒（HCV）感染仍然是一个全球性的健康问题。在此之前，我们小组评估了新型直接作用抗病毒药物（DAA）elbasvir 治疗 HCV 的 NS5A 耐药相关取代（RAS）的流行率，在西班牙将其引入临床应用之前。然而，西班牙 HCV-GT1a 的 NS5A 直接作用抗病毒药物的起源、流行历史、传播动态、多样性和基线 RAS 仍然未知。我们对慢性 HCV-G1a 感染且未使用 DAA 的个体进行了全国性的横断面调查。使用 HCV 群体测序、系统发育分析和贝叶斯方法。GT1a 分支 II 比分支 I 更为普遍（82.3%比 17.7%；P < 0.001），也更为古老（估计起源于 1912 年比 1952 年）。分支 II 的流行正在下降，而分支 I 的流行已达到平衡。共发现 58 种单一 RAS，占观察到的中度基线耐药（10%）水平。考虑到区域数据，观察到明显的差异，有 13 个地区显示中度水平（5-15%），一个地区显示高水平（20%）耐药。目前西班牙 HCV-GT1a 的流行是由分支 I 驱动的，分支 I 似乎与分支 II 有不同的传播途径。观察到对 NS5A-DAAs 的基线 RAS 处于中度水平，且不同地区存在明显差异。密切监测 DAA 治疗的反应将非常重要。
