Background: Hepatitis C virus (HCV) acts in the host as a complicated mixture of related variants with the potency to genetically escape host immune responses. Direct acting antivirals (DAAs) have been approved for HCV treatment with shorter duration, better cure rates and lower side effects. However, naturally occurring resistance associated substitutions (RASs) create some obstacles to this antiviral therapy success.

Objective: In this study, we aimed at the determination of the naturally occurring NS3/4A RASs in HCV/human immunodeficiency virus (HIV)infected patients.

Methods: A total of 120 DAA-naïve HCV-HIV co-infected patients were included. HCV NS3/4Agenome region was amplified with PCR and mutation analysis was performed by Sanger sequencing technique. The amino acid sequence diversity of the region was analyzed using geno2pheno HCV.

Results: Phylogenetic analysis showed that 73 cases were infected by 3a and 47 subjects by subtype1a. The overall RASs among studied subjects were observed in 6 (5%) individuals from 120 studied cases who were infected with HCV 1a. V36M/L, Q80L, S122G/L, R155T/G, A156S, D168Y/N and S174A/N/T mutations were detected in this study.

Conclusion: Although the prevalence of RASs was totally low in this study, the presence of several cases of double and triple mutants among this population suggests prior evaluation of protease inhibitors related mutations before initiation of standard treatment and also an investigation on a large population could be of high value.

背景：丙型肝炎病毒 (HCV) 在宿主中作为相关变体的复杂混合物起作用，具有遗传逃避宿主免疫反应的效力。直接作用抗病毒药物 (DAA) 已被批准用于 HCV 治疗，具有更短的持续时间、更好的治愈率和更低的副作用。然而，自然发生的耐药相关替代（RAS）对这种抗病毒治疗的成功造成了一些障碍。

目的：在本研究中，我们旨在确定 HCV/人类免疫缺陷病毒 (HIV) 感染患者中天然存在的 NS3/4A RAS。

方法：共纳入 120 名未接受 DAA 治疗的 HCV-HIV 合并感染患者。通过PCR扩增HCV NS3/4Agenome区域，并通过Sanger测序技术进行突变分析。使用geno2pheno HCV分析该区域的氨基酸序列多样性。

结果：系统发育分析显示3a型感染73例，1a亚型感染47例。在来自 120 个研究病例的 6 个（5%）感染 HCV 1a 的病例中观察到研究对象的总体 RAS。本研究检测到 V36M/L、Q80L、S122G/L、R155T/G、A156S、D168Y/N 和 S174A/N/T 突变。

结具有很高的价值。