基因1型HCV/HIV共同感染患者直接抗病毒药物预存耐药突变流行情况分析

Prevalence of pre-existing direct-acting antiviral agents resistance-associated variants in genotype 1 HCV/HIV co-infected patients

目的·探究基因1型丙型肝炎病毒(hepatitis C virus,HCV)/人类免疫缺陷病毒(human immunodeficiency virus,HIV)共同感染患者直接抗病毒药物(direct-acting antiviral agents,DAAs)预存耐药突变流行情况,以期对这一特殊群体的耐药情况有所了解。方法·通过美国国家生物技术信息中心(NCBI)核酸数据库进行数据挖掘,找出全部基因1型HCV/HIV共同感染患者的NS3和NS5B序列。然后用MEGA 5.0软件进行序列的比对和耐药分析。结果·总体来讲,无论基因1a型还是基因1b型,HCV/HIV共同感染患者NS3区的预存耐药突变流行率高(分别是26.06%和38.18%)。在基因1a型患者中,高耐药相关突变主要出现在Q80上(8.45%);而在基因1b型患者中,S122耐药突变最为常见(36.36%)。在NS5B区的预存耐药突变罕见(0.77%),尤其是在基因1a型患者中,没有1条序列检测到耐药相关突变。结论·基因1型HCV/HIV共同感染患者NS3区的预存耐药突变流行率高,但NS5B区的预存耐药突变罕见。对HCV/HIV共同感染这一特殊群体使用DAAs治疗时,以NS5B抑制剂为基础的联合方案是很有必要的。

Objective · To investigate the prevalence of pre-existing direct-acting antiviral agents（DAAs） resistance associated variants（RAVs） in genotype 1 hepatitis C virus（HCV）/human immunodeficiency virus（HIV） co-infected patients. Methods · All NS3 and NS5 B HCV sequences in genotype 1 HCV/HIV co-infected patients were retrieved from NCBI Gen Bank database. And sequences were aligned and analyzed using software MEGA 5.0. Results · In total, the overall prevalence of DAAs RAVs in NS3 region was high（26.06% and 38.18%, respectively）, no matter in genotype 1 a or genotype 1 b. In genotype 1 a, the high prevalence of RAVs mainly presented in the position Q80（8.45%）. In genotype 1 b, S122 RAV was most observed（36.36%）. It is worth noting that, RAVs in NS5 B region were rare observed（0.77%） in this study, especially as no RAV was detected in any sequence of genotype 1 a patients. Conclusion · The prevalence of pre-existing RAVs is high in NS3 region but rare in NS5 B region in HCV/HIV co-infected patients, suggesting that NS5 B inhibitors based combination regions are a better choice for HCV/HIV co-infected patients.