温州市新报告HIV-1感染者治疗前耐药分析

Pre-treatment drug resistance of newly reported HIV-1 infected individuals in Wenzhou

目的了解温州市2019年新报告艾滋病病毒Ⅰ型(HIV-1)感染者治疗前耐药(PDR)情况,为指导艾滋病抗病毒治疗提供依据。方法选择温州市2019年新报告的232例尚未经抗反转录病毒治疗(ART)的HIV-1感染者为研究对象,采集血浆样本,提取HIV-1病毒RNA,采用反转录PCR和巢式PCR扩增pol区基因并测序,分析耐药突变位点及对非核苷类反转录酶抑制剂(NNRTIs)、核苷类反转录酶抑制剂(NRTIs)和蛋白酶抑制剂(PIs)的耐药情况。结果获得199例未经ART治疗的HIV-1感染者的pol区基因序列,共检出8种基因亚型,以CRF07BC和CRF01AE为主,分别为94例和58例,占47.24%和29.15%;检出2种独特重组型毒株(URFs),分别为URF (CRF01AE/BC)和URF (B/C)。PDR 16例,检出率为8.04%。耐药位点突变31例,占15.58%;其中针对NNRTIs、NRTIs和PIs耐药突变位点分别检出20例、2例和9例,占64.52%、6.45%和29.03%。NNRTIs耐药位点突变包括K101E、K103N/R、V106I、E138K、V179D/E/T、Y181C、G190A和H221Y,4例病例同时出现2个耐药位点突变;NRTIs耐药位点突变为V75M和M184V;PIs耐药位点突变为M46I、L33F和Q58E。对我国新上市的NNRTIs新药多拉韦林(DOR)检出2例耐药病例。结论温州市2019年新报告HIV-1感染者PDR检出率为8.04%,以NNRTIs耐药为主;已出现对新药DOR的耐药,应加强耐药监测。

Objective To know the pre-treatment drug resistance(PDR) status of newly reported human immunodeficiency virus type 1(HIV-1) infected individuals in Wenzhou,so as to provide guidance for antiretroviral therapy(ART).Methods Totally 232 plasma samples of newly reported HIV-1 infected individuals who had not received ART were collected in Wenzhou in 2019.Virus(HIV-1) RNA was extracted,followed by reverse transcription PCR and nested PCR to amplify the pol region and sequence.Resistance mutations and resistance to non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleoside reverse transcriptase inhibitors(NRTIs) and protease inhibitors(PIs) was analyzed.Results The pol region sequences from 199 infected patients were obtained and the incidence of PDR was 8.04%(16/199).Eight genotypes were detected,including circulating recombinant forms(CRFs) CRF07BC(47.24%,94/199)and CRF01AE(29.15%,58/199) which were the dominant types.Two unique recombinant forms(URFs) were detected,namely URF(CRF01AE/BC) and URF(B/C).Thirty-one cases(15.58% 31/199) had drug-resistant mutations.For NNRTIs,NRTIs and PIs,20 cases(64.52%),2 cases(6.45%) and 9 cases(29.03%) with drug resistance mutations were detected,respectively.The resistance mutations to NNRTIs included K101E,K103N/R,V106I,E138K,V179 D/E/T,Y181C,G190A and H221Y.Four cases each had two resistance mutations to NNRTIs.The resistance mutations to NRTIs were V75 M and M184V.The resistance mutations to PIs were M46I,L33F and Q58E.For the newly released NNRTI drug Doravirine(DOR),two cases were found to have mutations of resistance.Conclusions The incidence of PDR among newly reported HIV-1 patients in Wenzhou is 8.04%,mainly caused by NNRTIs drug-resistant mutation.Resistance to the new drug DOR has emerged.The surveillance of drug resistance should continue to be strengthened.