广西新诊断HIV/AIDS患者HIV-1整合酶区基因突变及整合酶抑制剂耐药分析  

Analysis of gene mutations in the HIV-1 integrase region and resistance to integrase inhibitors in newly diagnosed HIV/AIDS patients in Guangxi

作　　者：严文霞 黄金萍[2] 陈荣凤 秦英梅[2] 黎彦君[2] 廖艳研 蒋俊俊[1,3] 梁丽娟 黄耀锋 黄丽静 梁浩[3] YAN Wen-xia;HUANG Jin-ping;CHEN Rong-feng;QIN Ying-mei;LI Yan-jun;LIAO Yan-yan;JIANG Jun-jun;LIANG Li-juan;HUANG Yao-feng;HUANG Li-jing;LIANG Hao(Guangxi Key Laboratory of AIDS Prevention and Treatment,Guangxi Medical University,Nanning,Guangxi 530021,China;不详)

机构地区：[1]广西医科大学公共卫生学院广西艾滋病防治研究点实验室,广西南宁530021 [2]南宁市第四人民医院,广西南宁530023 [3]广西医科大学生命科学研究院,广西南宁530021 [4]钦州市第一人民医院,广西钦州535000

出　　处：《现代预防医学》2023年第3期545-550,共6页Modern Preventive Medicine

基　　金：广西重点研发计划(桂科AB2018050022);广西壮族自治区卫健委自筹经费科研课题(Z20210498)。

摘　　要：目的 了解广西新诊断HIV-1感染者整合酶抑制剂(integrase stand transfer inhibitors,INSTIs)耐药率、HIV-1整合酶区耐药相关多态性位点的突变率及影响因素。方法 使用课题组2019年10月—2020年3月收集的广西新诊断HIV/AIDS患者血液样本,提取HIV-1整合酶区RNA、巢式PCR扩增整合酶基因并测序。利用斯坦福HIV耐药数据库确定患者HIV-1整合酶区耐药突变位点并计算患者耐药率。通过序列比对分析HIV-1整合酶区耐药相关多态性突变位点,使用多因素logistic回归分析HIV-1整合酶区耐药相关多态性位点发生突变的影响因素。结果 320例HIV-1患者的HIV-1整合酶区序列中,以CRF01_AE亚型(39.4%)为主,耐药率为2.19%,主要耐药突变位点为E92K(0.62%),次要耐药突变位点主要为E157Q(1.25%)。发生频率较高的HIV-1整合酶区耐药相关多态性位点有L74V(0.94%)、E138D(1.25%)和G163E(3.13%)。多因素logistic回归分析显示:HIV-1整合酶区耐药相关多态性突变的影响因素中,壮族是汉族的5.10倍(95%CI:1.81~18.26,P=0.005),CRF08_BC是CRF01_AE的2.90倍(95%CI:1.04~8.70,P=0.048)。结论 广西HIV-1新诊断感染者INSTIs耐药率水平较低,CRF08_BC亚型是HIV-1整合酶区耐药相关多态性位点突变的危险因素,应将INSTIs耐药监测纳入现有耐药监测工作中。Objective To investigate the prevalence of drug resistance to integrase stand transfer inhibitors(INSTIs), the rate of INSTIs polymorphic substitutions, and the influencing factors. Methods Blood samples of newly diagnosed HIV/AIDS individuals were collected from October 2019 to March 2020. The RNA of HIV-1 integrase region was extracted and the inte-grase gene was amplified by nested PCR and sequenced. The Stanford HIV-1 Drug Resistance database was used to interpret HIV-1 drug resistance mutations, and the rate of resistance INSTIs was calculated. The INSTIs polymorphic substitutions were analyzed by sequence alignment. Logistics regression was used to analyze factors of harboring INSTIs polymorphic substitutions. Results Sequences were obtained from 320 HIV-1 infected patients, of which 39.4% were of CRF01_AE subtype.The prevalence of resistance to INSTIs was 2.19%. The most common INSTIs mutation was E92K(0.62%), and the most common INSTIs secondary mutation was E198Q(1.25%). The most common INSTIs polymorphic substitutions were L74V(0.94%), E138D(1.25%), and G163E(3.13%). Results of multivariate logistic regression analysis showed that for the risk of harboring INSTIs polymorphic substitutions, individuals of Zhuang ethnicity had 5.10 times higher risk than that of Han ethnicity(95%CI: 1.81-18.26, P=0.005), and CRF08_BC was 2.90 times higher than CRF01_AE(95%CI:1.04-8.70, P=0.048).Conclusion Primary drug resistance to INSTIs is low in the study population. The patients infected with CRF08_BC subtype is associated with harboring INSTIs polymorphic substitutions. The results emphasize the need to add INSTIs resistance testing into the current HIV drug resistance surveillance.

关 键 词：人类免疫缺陷病毒 整合酶抑制剂 耐药 基因多态性 

分 类 号：R512.91[医药卫生—内科学] R914[医药卫生—临床医学]