摘要: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 sam-ples 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 previ-ous paid blood donors with HCV/HIV-1 co-infection, 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.