HCV基因型1人群耐药相关变异

用直接作用抗病毒药物(DAAs)治疗HCV持续时间短，副作用少，非常有效。然而，并非所有患者都可以单独使用DAAs治疗，因为某些基因型需要聚乙二醇化干扰素和/或利巴韦林。因此，准确的基因分型仍然是治疗选择的支柱之一。随着越来越多的DAAs进入市场，耐药相关变异(RAVs)的检测对于进一步完善和优化药物治疗变得越来越重要。在这项研究中，我们专门调查了全球流行的HCV基因型(GT1)中出现的RAVs。110份来自亚洲慢性HCV GT1a (n=56)或GT1b (n=54)感染患者的edta血浆和血清样本纳入本研究。我们使用了一种新型的自动化下一代测序(NGS)集成工作流程，包括机器人平台、RNA提取和文库准备试剂盒(圣淘沙SQ HCV基因分型检测)、Ion Torrent深度测序和软件。系统基于专有软件自动生成报表。测序数据分析包括NS3、NS5A和NS5B基因中已知的136个RAVs。52.7%(58/110)的HCV GT1a和GT1b株在所有靶基因的23个位点上携带1个或多个RAVs。 An unequal distribution of 4 mutations in the GT1 subtypes was observed. The frequency of the Q80K mutation (NS3) was 25%(14/56) in GT1a and 1.9%(1/54) in GT1b while mutations Q54H and Y93H (NS5A) were prevalent in GT1b at 42.6%(23/54) and 18.5%(10/54) respectively. Y93H was detected in GT1a at 1.8%(1/56). Mutation V499A in NS5B was only found in GT1b at 25.9%(14/54), but not in GT1a. In conclusion, beyond the crucial role of accurate HCV genotyping detection of RAVs by NGS across drug target genes is becoming increasingly important for fine-tuning of HCV treatment. A combined approach by a newly developed NGS-based system can help to streamline generation of relevant pre-treatment information.