重庆市2014年至2018年人类免疫缺陷病毒1型感染者的耐药突变分析  

Analysis of drug-resistant mutations in human immunodeficiency virus-1 infected patients in Chongqing City from 2014 to 2018

作　　者：李梅[1] 李俊刚 罗福龙 王静[2] 陈耀凯[1] 韩梅 邓仁麑 Li Mei;Li Jungang;Luo Fulong;Wang Jing;Chen Yaokai;Han Mei;Deng Renni(Central Laboratory,Chongqing Infectious Disease Medical Center,Chongqing 400036,China;Department of Clinical Laboratory,Chongqing Infectious Disease Medical Center,Chongqing 400036,China)

机构地区：[1]重庆市公共卫生医疗救治中心中心实验室,400036 [2]重庆市公共卫生医疗救治中心医学检验科,400036

出　　处：《中华传染病杂志》2020年第5期283-287,共5页Chinese Journal of Infectious Diseases

基　　金：重庆市卫生计生委医学科研重点项目(2016ZDXM033)。

摘　　要：目的:了解重庆市2014年至2018年接受高效抗反转录病毒治疗的人类免疫缺陷病毒1型(human immunodeficiency virus-1,HIV-1)感染者耐药突变情况。方法:收集2014年5月至2018年12月在重庆市公共卫生医疗救治中心进行高效抗反转录病毒治疗6个月以上的HIV-1感染者880例,采集其血浆标本,使用一步法反转录聚合酶链反应(polymerase chain reaction,PCR)和巢式PCR扩增HIV-1 pol基因区的蛋白酶及反转录酶区,获得的扩增序列与耐药数据库对比进行HIV-1基因型耐药分析。采用病毒基因分型工具软件分析HIV-1亚型分布。计数资料比较采用χ^2检验。结果:880例患者中,血浆HIV-1病毒载量为(4.12±0.63)lg拷贝/mL;CD4^+T淋巴细胞计数为(251±124)/μL;抗病毒治疗中位时间为26个月。亚型分析中,重组型(circulating recombinant form,CRF)01-AE亚型在HIV-1亚型中占比最大,为38.9%(342/880),CRF07-BC亚型占28.5%(251/880),B+C亚型占16.2%(143/880)。其中534例患者存在耐药突变,总耐药率为60.7%。对核苷类反转录酶抑制剂(nucleoside reverse transcriptase inhibitor,NRTI)、非核苷类反转录酶抑制剂(non-nucleoside reverse transcriptase inhibitor,NNRTI)和蛋白酶抑制剂(protease inhibitor,PI)的耐药率分别为51.0%(449/880)、58.6%(516/880)和1.7%(15/880)。对拉米夫定、恩曲他滨、依非韦仑和奈韦拉平的耐药较为严重,中高度耐药率分别为46.8%(412/880)、46.8%(412/880)、51.3%(451/880)和53.6%(472/880);而对齐多夫定(6.0%,53/880)、依曲韦林(9.0%,79/880)和PI类药物的耐药情况尚不严重。NRTI最常见的耐药突变位点为M184IV(47.3%)、K65R(22.2%)和K70RE(12.6%);NNRTI为K103NS(25.1%)、V106A(19.7%)和V179DE(14.4%);PI为L10FIV(7.4%)和A71IVT(6.5%)。CRF01-AE亚型的耐药率为69.3%(237/342)高于CRF07-BC亚型的49.8%(125/251)和B+C型的51.0%(73/143),差异均有统计学意义(χ^2=22.6、14.6,均P<0.05)。结论:重庆市HIV-1感染者经高效抗反转录病毒治疗6个月后,耐药发生�Objective To investigate the drug-resistant mutations of human immunodeficiency virus-1(HIV-1)in patients who received highly active antiretroviral therapy(HAART)from 2014 to 2018.Methods A total of 880 patients with HIV-1 infection who had been treated with HAART for more than six months in Chongqing Infectious Disease Medical Center from May 2014 to December 2018 were enrolled.Plasma samples were collected,and one-step reverse transcription-polymerase chain reaction(PCR)and nested PCR were taken to amplify protease and reverse transcriptase regions of HIV-1 pol gene region.The obtained amplified nucleotide sequences were compared with the drug resistance database for antiviral drug resistance analysis.Viral genotyping tool software was used to analyze HIV-1 subtype distribution.The categorical variables were compared using chi-square test.Results Among 880 patients,the plasma HIV-1 viral load was(4.12±0.63)lg copies/mL,the CD4^+T lymphocyte count was(251±124)/μL,and the median duration of antiviral therapy was 26 months.In the subtypes analysis,the circulating recombinant form(CRF)01-AE subtype was the largest proportion of HIV-1 subtypes,accounting for 38.9%(342/880),and the CRF07-BC subtype accounted for 28.5%(251/880),B+C subtypes accounted for 16.2%(143/880).Drug-resistant mutations were detected in 534 patients,with a total drug resistance rate of 60.7%.The drug resistance rates of nucleoside reverse transcriptase inhibitors(NRTI),non-nucleoside reverse transcriptase inhibitors(NNRTI)and protease inhibitors(PI)were 51.0%(449/880),58.6%(516/880)and 1.7%(15/880),respectively.The drug resistances to lamivudine,emtricitabine,efavirenz,and nevirapine were serious,and the medium/high resistance rates were 46.8%(412/880),46.8%(412/880),51.3%(451/880),and 53.6%(472/880),respectively,while those to zidomidudine(6.0%,53/880),etravirin(9.0%,451/880)and PI were not serious.M184IV(47.3%),K65R(22.2%)and K70RE(12.6%)were the most frequent mutations for NRTI.K103NS(25.1%),V106A(19.7%)and V179DE(14.4%)were the most freq

关 键 词：人类免疫缺陷病毒 抗反转录病毒治疗 高效 抗药性 突变 

分 类 号：R512.91[医药卫生—内科学] R978.7[医药卫生—临床医学]