摘要
目的调查北京市1型艾滋病病毒(HIV-1)新发感染者的病毒毒株中反转录酶抑制剂、蛋白酶抑制剂(PI)以及整合酶抑制剂(INTI)原发性耐药情况,为临床治疗提供参考依据。方法收集2019年214例未接受抗病毒治疗的HIV-1感染者外周静脉血血浆,提取HIV-核糖核酸(RNA),通过巢式聚合酶链式反应扩增HIV-1的pol基因区进行序列测定,分析耐药突变位点以及抗病毒药物(ARV)耐药情况。结果214例未经抗病毒治疗的HIV-1感染者血浆成功扩增206例,包括A亚型、B亚型、C亚型、B+C亚型、CRF01_AE亚型、CRF07_BC亚型、以及CRF5501_B亚型,均为国内常见亚型。34例出现耐药突变位点,其中6例出现至少一种ARV低度及以上耐药的总体耐药率为2.9%(6/206)。核苷类反转录酶抑制剂(NRTI)、非核苷类反转录酶抑制剂(NNRTI)、PI和INTI耐药位点突变频率分别为0例、23例、9例、2例,其中NNRTI耐药相关的突变位点为V179D/L、V179E、V106I、E138A、E138G、K103R。PI耐药相关的突变位点为Q58E,M46L和L33F。INTI耐药相关突变位点为E157Q和T97A。尚未在国内上市的新药多拉韦林(DOR)出现1例低度耐药,与V106I位点突变相关。结论北京地区整体HIV-1传播性耐药仍然处于世界卫生组织低警戒线水平,以NNRTI相关耐药为主,未在中国上市的NNRTI药物DOR也发现了耐药。
Objective To investigate the primary drug resistance of reverse transcriptase inhibitors,protease inhibitors(PI)and integrase inhibitors(INTI)in the viral strains of newly infected HIV-1 patients in Beijing,and to provide reference for clinical treatment.Methods Peripheral venous blood plasma of 214 HIV-1 infected patients without antiviral treatment(ART)was collected in 2019,and HIV-RNA was extracted.The pol gene region of HIV-1 virus was amplified by nested polymerase chain reaction for sequencing.Results 206 cases of 214 HIV-1 infected patients without ART were successfully amplified in plasma,including subtypes of A,B,C,B+C,CRF01_AE,CRF07_BC,and CRF5501_B,all of which were common subtypes in China.Analysis of drug resistance:34 cases showed mutation sites of drug resistance,among which 6 cases showed low or higher resistance to at least one ARV,with an overall drug resistance rate of 2.9%(6/206).The mutation frequencies of nucleoside reverse transcriptase inhibitors(NRTI),non-nucleoside reverse transcriptase inhibitors(NNRTI),PI and INTI resistance sites were 0,23,9,2 cases,respectively,among which the mutation sites associated with NNRTI resistance were V179 D/E/L,V106 I,E138 A,E138 G,K103 R.The mutation sites associated with PI resistance were Q58 E,M46 L and L33 F.The mutants associated with drug resistance in INTI were E157 Q and T92 A.A new drug,Dorivirine(DOR),which has not yet been marketed in China,showed low drug resistance in 1 case,which was associated with mutation of V106 I site.Conclusion The overall primary drug resistance of HIV-1 in Beijing is still at the low level of WHO’s warning line.It is mainly NNRTI-related resistance.DOR resistance to NNRTI drug not yet marketed in China has been found.
作者
谢小慧
于凤婷
张霞
赵红心
张福杰
XIE Xiaohui;YU Fengting;ZHANG Xia;ZHAO Hongxin;ZHANG Fujie(Ditan Teaching Hospital of Peking University,Beijing100015,China;Beijing Ditan Hospital Affiliated to Capital Medical University,Beijing 100015;Medical Laboratory Science Department of Weifang Medical College,Shandong 261053)
出处
《中国艾滋病性病》
CAS
CSCD
北大核心
2020年第6期579-583,共5页
Chinese Journal of Aids & STD
基金
国家“十三五”重大专项(2017ZX10202102-005-003,2018ZX10721102-003-003,2018ZX10302-102,2018ZX10301-407-005,2018ZX10302103-001-003,2017ZX10202101-004-001)
北京市医管中心项目(DFL20191802)。
关键词
艾滋病病毒
传播性耐药
整合酶抑制剂耐药
HIV
primary resistance
integrase inhibitor resistance
Dorivirine(DOR)