既往有偿献血HIV-1感染者中合并感染的HCV对telaprevir和boceprevir天然耐药分析

Naturally occurring HCV resistance to telaprevir and boceprevir in previous paid blood donors with HCV/HIV-1 co-infection

目的分析既往有偿献血人群HIV-1感染者中合并感染的HCV对telaprevir和boceprevir的天然耐药,为HCV的耐药监测及临床抗病毒治疗提供基础数据。方法收集既往有偿献血人群HIV阳性患者的血浆样本,检测其HCV抗体,应用巢式PCR扩增HCV NS3/4A区,对测序结果进行耐药分析,计算耐药率,评价耐药毒株的流行趋势。结果从150份符合要求的样本里共获得70份(46.67%)HCV NS3/4A基因序列。检测出耐药相关突变4例(5.71%),其中对boceprevir耐药2例(2.86%),耐药位点为R117H和A156V;对telaprevir耐药2例(2.86%),耐药位点为R117H和A156V;对telaprevir可能耐药2例(2.86%),耐药位点为T54S。尚未发现V36A/M/L/C、Q41H/R、F43C/S、T54A、V55A、Q80R、R109K、S138C、R155G/I/K/M/T/Q/S、A156S/T、D168A/E/G/H、V170A/T/I、N174G/S、L175M等已报道的耐药位点。其他突变中,氨基酸替换率超过90%的变异位点有I35V、A40T、R62K、I64L、V71I、S66G、S91A和T42S;在系统进化树中,耐药序列呈点状散在分布,未发现聚集性。结论既往有偿献血HIV-1感染者中合并感染的HCV对telaprevir和boceprevir存在天然耐药,耐药相关突变率分别为5.71%和2.86%。其他氨基酸位点出现突变率较高,但是未发现与耐药相关。各耐药菌株之间未发现传播关联性。

Objective To analyze naturally occurring HCV resistance to telaprevir and boceprevir in previous paid blood donors with HCV/HIV-1 co-infection, and provide basic data for drug monitoring and antiviral therapy for HCV. Methods Plasma samples were collected from previous paid blood donors with HIV-1 infection, and HCV antibodies were detected. The HCV NS3/4A region was amplified using nested PCR, and drug resistance analysis was made by calculating resistance rate and assessing the prevalence of resistant strains. Results A total of 70 （46.67%） fragments containing HCV NS3/4A region were successfully ampli-fied from 150 samples. Drug resistance-related mutations were detected in 4 （5.71%） patients, resistance to boceprevir in 2 patients （2.86%）, with the resistance loci of R117H and A156V, and resistance to telaprevir in 2 （2.86%） patients, with the resistance loci of R117H and A156V; possible resistance to telaprevir was found in 2 （2.86%） patients, with the resistance locus of T54S. Previously reported resistance loci, such as V36A/M/L/C, Q41H/R, F43C/S, T54A, V55A, Q80R, R109K, S138C, R155G/I/K/M/T/Q/S, A156S/T, D168A/E/G/H, V170A/T/I, N174G/S and L175M, were not detected. I35V, A40T, R62K, I64L, V71I, S66G, S91A and T42S exhi-bited a high replacement rate of over 90%. Phylogenetic analysis showed that drug resistance loci were scatteredly distributed in the phylogeny tree, and no aggregation was detected. Conclusions HCV resistance to telaprevir and boceprevir occurs naturally in previous paid blood donors with HCV/HIV-1 coinfection, with the resistance rates of 5.71% and 2.86%, respectively. Other loci exhibit high mutation rates, but no correlation with drug resistance is found. Moreover, no correlation is found among the resistant strains.