HIV-1 感染者抗病毒治疗后耐药突变与影响因素分析  

Drug Resistance Mutations and Influencing Factors in HIV-1-Infected Patients Experiencingthe Failure of Antiretroviral Therapy

作　　者：张鑫愉 刘萌 唐湘云 李维民 马峰 李岩[2] 王莹莹[2] 安宁 路新利 ZHANG Xinyu;LIU Meng;TANG Xiangyun;LI Weimin;MA Feng;LI Yan;WANG Yingying;AN Ning;LU Xinli(College of Public Health,Hebei Medical University,Shijiazhuang 050017,China;Department of AIDS Research,Hebei Provincial Center for Disease Control and Prevention,Shijiazhuang 050021,China;Hengshui Center for Disease Control and Prevention,Hengshui 053099,China;College of Public Health,North China University of Science and Technology,Tangshan 063210,China)

机构地区：[1]河北医科大学公共卫生学院,河北石家庄050017 [2]河北省疾病预防控制中心艾滋病所,河北石家庄050021 [3]衡水市疾病预防控制中心艾滋病所,河北衡水053099 [4]华北理工大学公共卫生学院,河北唐山063210

出　　处：《中国皮肤性病学杂志》2023年第10期1164-1170,共7页The Chinese Journal of Dermatovenereology

基　　金：河北省医学科学研究重点课题计划项目(20160061)。

摘　　要：目的对河北地区治疗失败HIV-1感染者体内获得性耐药基因的突变情况进行调查,分析其影响因素。方法收集河北省2019年1—12月抗病毒治疗后病毒载量≥1000 CPs/mL HIV-1感染者的人口社会学信息及血浆标本,通过巢式反转录聚合酶链反应扩增HIV-1 pol基因序列,将测序结果与美国斯坦福大学HIV耐药数据库比对,分析HIV-1感染者耐药基因突变情况及影响因素。结果获得性耐药发生率为76.47%(104/136),其中94.23%(98/104)对非核苷类逆转录酶抑制剂耐药,EFV(依非韦伦)和NVP(奈韦拉平)耐药率高且多呈现高度耐药,主要突变位点为K103N、V106M和Y181C;68.26%(71/104)对核苷类逆转录酶抑制剂耐药,3TC(拉米夫定)和FTC(恩曲他滨)高度耐药最严重,主要突变位点为M184V/I。患者多选择一线药物为治疗方案(68.38%,93/136),非核苷类逆转录酶抑制剂(NNRTIs)和核苷类逆转录酶抑制剂(NRTIs)的耐药差异有统计学意义(P<0.05)。Logistics回归分析显示民族和传播途径是影响耐药发生的独立危险因素,无危险因素进入多因素Logistics回归模型。结论获得性耐药成为治疗失败的主要原因,应尽早对感染者进行耐药监测,有针对性的使用药物,提高治疗效果。Objective The mutations in acquired drug resistance genes and influencing factors were examined in HIV-1-infected patients with treatment failure.Methods Demographic and sociological data were investigated via a questionnaire survey,and plasma specimens were collected from patients with viral load≥1000 CPs/mL from January to December 2019 in Hebei province.The HIV-1 pol gene(1.3 kb)was amplified by nested reverse transcription polymerase chain reaction,and the sequencing results were submitted to the HIV drug resistance database(https://hivdb.stanford.edu/)to analyze the mutations of drug resistance genes and influencing factors.There were significant differences in drug resistance between NNRTIs and NRTIs(P<0.05).Results The incidence of acquired drug resistance among HIV-1-infected patients who experienced antiviral therapy failure was 76.47%(104/136).Of the 136 patients,104 had drug-resistance mutations.Of patients with drug resistance,94.23%(98/104)were resistant to non-nucleoside reverse transcriptase inhibitors,with the most frequent resistance to EFV(efavirenz)and NVP(nevirapine).The primary mutation sites were K103N,V106M and Y181C;68.26%(71/104)patients were resistant to nucleoside reverse transcriptase inhibitors,with the most often occurring resistance to 3TC(lamivudine)and FTC(emtricitabine).The main mutation site was M184V/I.Most patients used first-line drugs as treatment options(68.38%,93/136).Logistic regression analysis indicated that ethnicity and transmission routes were independent risk factors for drug resistance.Conclusion Acquired drug resistance has become a major factor in treatment failure for HIV-1 patients.We should monitor drug resistance among HIV-1 infected patients as early as possible and use drugs in a targeted manner to improve the effectiveness of treatment.

关 键 词：艾滋病 流行特征 耐药 抗病毒治疗 

分 类 号：R512.91[医药卫生—内科学]