| HCV耐药突变在三个Ⅰb期临床试验中对DAA单药给药后短期疗效影响的分析 |
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| 引用本文： | 周景,张洪,李晓娇,宋相仕,张萌萌,丁艳华. HCV耐药突变在三个Ⅰb期临床试验中对DAA单药给药后短期疗效影响的分析[J]. 中国药学, 2021, 30(2): 133-145. DOI: 10.5246/jcps.2021.02.011 |
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| 作者姓名： | 周景 张洪 李晓娇 宋相仕 张萌萌 丁艳华 |
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| 摘 要： | 耐药相关突变(Resistance-associated substitutions,RASs)是丙型肝炎病毒(Hepatitis C virus,HCV)治疗的关键因素,并与一些直接抗病毒药物(Direct acting antivirals,DAAs)为基础的治疗方案的治疗结果相关.在本研究中,我们主要分析了三个Ⅰ...
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| 关 键 词： | 直接抗病毒药物 耐药相关突变 HCV测序 基因型1b和2a NS5A抑制剂 |
| 收稿时间： | 2020-09-18 |
Analysis of the effect of HCV resistance-associated substitutions on the short-term efficacy of DAA after single administration in three phase Ib clinical trials |
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| Jing Zhou,Hong Zhang,Xiaojiao Li,Xiangshi Song,Mengmeng Zhang,Yanhua Ding. Analysis of the effect of HCV resistance-associated substitutions on the short-term efficacy of DAA after single administration in three phase Ib clinical trials[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(2): 133-145. DOI: 10.5246/jcps.2021.02.011 |
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| Authors: | Jing Zhou Hong Zhang Xiaojiao Li Xiangshi Song Mengmeng Zhang Yanhua Ding |
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| Abstract: | As crucial factors in hepatitis C virus (HCV) management, resistance-associated substitutions (RASs) are associated with the treatment outcome of some direct-acting antiviral (DAA)-based regimens. In this study, we mainly analyzed the impact of baseline Y93H or Y93Y/H on the short-term efficacy after single administration of NS5A inhibitors in three phase Ib clinical trials (yimitasvir phosphate, KW-136 and fopitasvir), and analyzed the prevalence of baseline RASs and treatment-emergent RASs. A total of 94 treatment-na?ve HCV genotype (GT)-1b (n = 63) and GT-2a (n = 31) Chinese patients were enrolled in three phase 1b clinical trials. We investigated RASs in 77 patients with next generation or Sanger sequencing. In the 7-day trial of yimitasvir phosphate, the mean maximum HCV RNA decrease of patients with baseline Y93H or Y93Y/H was lower than that of patients without the mutation in the 30 mg and 200 mg cohorts (0.83 vs. 2.45 log10 IU/mL and 1.92 vs. 2.63 log10 IU/mL). In the 3-day trial of KW-136, the mean maximum HCV RNA decrease in patients with baseline Y93H or Y93Y/H was lower than that of patients without the mutation in the 30, 60 and 120 mg cohorts (1.58 vs. 2.89 log10 IU/mL, 3.16 vs. 4.09 log10 IU/mL and 3.00 vs. 5.04 log10 IU/mL, respectively). In the 3-day trial of fopitasvir, only 30 mg group had baseline Y93H or Y93Y/H, and the average maximum HCV RNA decrease of patients with baseline Y93H or Y93Y/H was lower than that of patients without the mutation (1.45 vs. 3.59 log10 IU/mL). In the three trials, baseline RASs were observed in 54 patients (70.1%; 54/77). The most prevalent baseline RASs were Y93H and Y93Y/H (18.2%; 14/77), followed by L31M (16.9%; 13/77). The most common RASs after single administration of DAA were Y93H and Y93Y/H. Our data could provide reference for future clinical treatment and clinical trial. |
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| Keywords: | Direct acting antiviral agents Resistance-associated substitutions HCV sequencing Genotype 1b and 2a HCV NS5A inhibitors |
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