Li Zhao, Chen Zhi-Wei, Li Hu, Ren Hong, Hu Peng
Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Infect Drug Resist. 2017 Oct 31;10:377-392. doi: 10.2147/IDR.S146595. eCollection 2017.
Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) are potent and highly efficacious. However, resistance-associated substitutions (RASs) relevant to DAAs can impair treatment effectiveness even at baseline. Moreover, the prevalence of baseline RASs in HCV genotype 1b-infected patients in western China is still unclear.
Direct sequencing of the HCV NS3, NS5A, and NS5B regions was performed in baseline serum samples of 70 DAAs treatment-naïve HCV 1b-infected patients in western China. The sequences were analyzed with MEGA version 5.05 software. Evolutionary patterns of RASs and amino-acid covariance patterns in the , , and genes were analyzed by MEGA and Cytoscape (version 3.2.1), respectively.
The presence of at least one RAS in the NS3 region (C16S, T54S, Q80R/L, A87T, R117H, S122G, V132I, V170I) was observed in 85.48% (53 of 62) of patients, RASs in the NS5A region (L28M, R30Q, Q54H, P58S/T, Q62H/R, Y93H) were observed in 42.42% (28 of 66) of patients, and RASs in the NS5B region (N142S, A300T, C316N, A338V, S365A, L392I, M414L, I424V, A442T, V499A, S556G) were observed in 100% (44 of 44) of patients. Evolutionary patterns of RASs and amino-acid covariance patterns for the , , and genes are reported.
The prevalence of RASs relevant to DAAs detected in the NS3, NS5A, and NS5B regions of HCV 1b from DAA treatment-naïve patients is high. Therefore, more attention should be paid to RASs associated with DAAs in the upcoming DAA-treatment era in China.
针对丙型肝炎病毒(HCV)的直接作用抗病毒药物(DAA)效力强大且疗效显著。然而,与DAA相关的耐药相关替代(RAS)即使在基线时也可能损害治疗效果。此外,中国西部HCV 1b基因型感染患者中基线RAS的流行情况仍不清楚。
对中国西部70例初治DAA的HCV 1b感染患者的基线血清样本进行HCV NS3、NS5A和NS5B区域的直接测序。使用MEGA 5.05软件对序列进行分析。分别通过MEGA和Cytoscape(3.2.1版)分析NS3、NS5A和NS5B基因中RAS的进化模式和氨基酸协方差模式。
在85.48%(62例中的53例)的患者中观察到NS3区域存在至少一种RAS(C16S、T54S、Q80R/L、A87T、R117H、S122G、V132I、V170I),在42.42%(66例中的28例)的患者中观察到NS5A区域的RAS(L28M、R30Q、Q54H、P58S/T、Q62H/R、Y93H),在100%(44例中的44例)的患者中观察到NS5B区域的RAS(N142S、A300T、C316N、A338V、S365A、L392I、M414L、I424V、A442T、V499A、S556G)。报告了NS3、NS5A和NS5B基因的RAS进化模式和氨基酸协方差模式。
在初治DAA患者的HCV 1b的NS3、NS5A和NS5B区域中检测到的与DAA相关的RAS流行率很高。因此,在中国即将到来的DAA治疗时代,应更加关注与DAA相关的RAS。