Department of Zoology, University of Peshawar, Peshawar, Khyber Pakhtunkhwa, Pakistan.
Department of Medicine, Khyber Teaching Hospital, Peshawar, Khyber Pakhtunkhwa, Pakistan.
PLoS One. 2020 Apr 10;15(4):e0231480. doi: 10.1371/journal.pone.0231480. eCollection 2020.
Chronic Hepatitis C Virus (HCV) infection is still a major health issue especially in endemic areas where fewer direct-acting virals (DAAs) are treatment options. Some HCV variants are associated with resistance and it reduces DAAs success where pre-existing variants prevail. In this study, we investigated resistance-associated polymorphisms (RAPs) in the HCV NS3 region from DAAs naïve Pakistani patients. 277 chronic HCV treatment naïve patients infected with genotype 1a, 3a and 3b were selected from various clinical centers in the capital city of Khyber Pakhtunkhwa province Pakistan. All the patients were included in this study after taking informed consent. HCV NS3 region was amplified and Sanger sequencing was performed to analyze RAPs to NS3 protease inhibitors. Of the total 29.24% (81/277) patients had detected with known RAPs viz V36A/G/L, T54S, V55A/D/I, Q80K/R, S122G/T/R, R155K/T/I, V158I, D168T/Q, and I170V. Among HCV-1a subjects overall RAPs found were 26.09% (12/46) and most prevalent substitutions were V36A/G (10.87%, 5/46) and R155K/T/I (8.70%, 4/46). Of the total HCV-3a infected patients, 30.95% were observed with RAPS. Ammon these, the most frequent substitutions were Q80R (13.69%, 23/168) followed by V36L (18.33%, 14/168) and V55I (5.95%, 10/168). Among HCV-3b patients, 26.98% were found with RAPs and S122R and Q80R were the dominant variants detected in 17.46 (11/63) and 12.70% (8/63) patients respectively. All these substitutions were associated with Boceprevir, Simeprevir, Telaprevir, and Paritaprevir. Single substitution in one sequence was found in 18.77% (52/277) and multiple in 10.46% (29/277). More than one RAP was frequent in HCV-3a sequences. Natural RAPs are common in chronic HCV patients infected with genotype 1a, 3a and 3b, the most prevalent subtypes in Pakistan. High prevalence of HCV NS3 RAPs suggested a large scale study of the NS3 gene before the introduction of NS3 protease inhibitors in Pakistan.
慢性丙型肝炎病毒 (HCV) 感染仍然是一个主要的健康问题，尤其是在流行地区，那里可供选择的直接作用抗病毒药物 (DAAs) 较少。一些 HCV 变体与耐药性有关，这降低了 DAAs 的成功率，因为先前存在的变体占主导地位。在这项研究中，我们研究了来自巴基斯坦无 DAA 治疗经验的 HCV 患者的 HCV NS3 区域中的耐药相关突变 (RAPs)。从巴基斯坦开伯尔-普赫图赫瓦省省会的各个临床中心选择了 277 名未经治疗的慢性 HCV 治疗初治患者，他们均感染了基因型 1a、3a 和 3b。在获得知情同意后，所有患者均被纳入本研究。扩增 HCV NS3 区域并进行 Sanger 测序，以分析 NS3 蛋白酶抑制剂的 RAPs。在总共 29.24%（81/277）的患者中检测到了已知的 RAPs，即 V36A/G/L、T54S、V55A/D/I、Q80K/R、S122G/T/R、R155K/T/I、V158I、D168T/Q 和 I170V。在 HCV-1a 受试者中，总的 RAPs 发现率为 26.09%（12/46），最常见的取代是 V36A/G（10.87%，5/46）和 R155K/T/I（8.70%，4/46）。在感染 HCV-3a 的患者中，有 30.95%的患者出现了 RAPS。在这些患者中，最常见的取代是 Q80R（13.69%，23/168），其次是 V36L（18.33%，14/168）和 V55I（5.95%，10/168）。在 HCV-3b 患者中，有 26.98%的患者发现了 RAPs，S122R 和 Q80R 是检测到的优势变异，分别占 17.46%（11/63）和 12.70%（8/63）。所有这些取代都与 Boceprevir、Simeprevir、Telaprevir 和 Paritaprevir 有关。在 18.77%（52/277）的序列中发现了单个取代，在 10.46%（29/277）的序列中发现了多个取代。HCV-3a 序列中多次出现 RAP。在感染基因型 1a、3a 和 3b 的慢性 HCV 患者中，天然 RAPs 很常见，这是巴基斯坦最常见的亚型。HCV NS3 RAPs 的高流行率表明，在巴基斯坦引入 NS3 蛋白酶抑制剂之前，需要对 NS3 基因进行大规模研究。
