河南省2018年至2022年抗反转录病毒治疗失败的人类免疫缺陷病毒感染/艾滋病患者基因型耐药的影响因素  

Influencing factors of genotypic drug resistance in people living with human immunodeficiency virus/acquired immunodeficiency syndrome who failed anti-retroviral therapy in Henan Province from 2018 to 2022

作　　者：孙燕[1] 陈昭云[2] 霍玉奇[3] 冯梦瑶 刘金瑾 杨萱[1] 赵清霞[1] 张晓华[1] 赵淑娴[1] 张雪[1] 王艳[1] Sun Yan;Chen Zhaoyun;Huo Yuqi;Feng Mengyao;Liu Jinjin;Yang Xuan;Zhao Qingxia;Zhang Xiaohua;Zhao Shuxian;Zhang Xue;Wang Yan(Department of Infection,The Sixth People′s Hospital of Zhengzhou,Zhengzhou 450015,China;Clinical Research Center,The Sixth People′s Hospital of Zhengzhou,Zhengzhou 450015,China;Center for Translational Medicine Research,The Sixth People′s Hospital of Zhengzhou,Zhengzhou 450015,China)

机构地区：[1]郑州市第六人民医院感染科,郑州450015 [2]郑州市第六人民医院临床医学研究中心,郑州450015 [3]郑州市第六人民医院转化医学研究中心,郑州450015

出　　处：《中华传染病杂志》2024年第4期219-224,共6页Chinese Journal of Infectious Diseases

基　　金：河南省医学科技攻关省部共建项目(SB201903030);2023年河南省重点研发与推广专项(232102311081)。

摘　　要：目的分析河南省抗反转录病毒治疗(ART)失败的人类免疫缺陷病毒(HIV)感染/艾滋病(AIDS)患者基因型耐药的情况及其影响因素,为调整ART方案、减少耐药提供依据。方法纳入2018年1月至2022年12月河南省接受ART 24周以上并出现病毒学失败(HIV RNA≥500拷贝/mL)的HIV感染/AIDS患者,收集基线CD4+T淋巴细胞计数、ART方案等临床资料,并于郑州市第六人民医院进行HIV-1基因亚型及其耐药序列突变检测,将序列提交美国斯坦福大学HIV耐药解释系统比对检测结果,确定对核苷类反转录酶抑制剂(NRTI)、非核苷类反转录酶抑制剂(NNRTI)、蛋白酶抑制剂(PI)、整合酶抑制剂(INSTI)的基因型耐药结果。采用多因素logistic回归分析ART失败患者发生耐药的影响因素。结果982例HIV感染/AIDS患者中899例成功扩增获得序列,检出耐药737例,耐药率为81.98%(737/899),其中对NRTI、NNRTI、PI、INSTI的耐药率分别为71.97%(647/899)、79.31%(713/899)、5.23%(47/899)和2.72%(20/734)。737例耐药患者中发生2类药物同时耐药者最多,占79.78%(588/737),主要为NRTI+NNRTI耐药[79.10%(583/737)];99例(13.43%)仅发生1类药物耐药,48例(6.51%)发生3类药物同时耐药,2例(0.27%)对上述4类药物均耐药。共检测到10种HIV-1基因亚型,其中B亚型最多,占59.73%(537/899),其次为流行重组型(CRF)01AE亚型[21.91%(197/899)]和CRF07BC亚型[9.45%(85/899)]。基线CD4+T淋巴细胞计数、ART方案和HIV-1基因亚型是耐药发生的独立危险因素,基线CD4+T淋巴细胞计数<100/μL的患者发生耐药的风险是CD4+T淋巴细胞计数≥250/μL的4.55倍[95%可信区间(CI)2.69~7.70];使用2NRTIs+NNRTI方案的患者发生耐药的风险是使用2NRTIs+INSTI方案的4.51倍(95%CI 1.75~11.63);感染B亚型和CRF01AE亚型的患者发生耐药的风险分别是感染CRF07BC亚型的2.18倍(95%CI 1.10~4.29)和2.70倍(95%CI 1.26~5.78)。结论河南省ART失败的HIV感染/AIDS患者基因型耐药发生率较高,基线低CObjective To analyze the influencing factors of genotypic drug resistance mutations in people living with human immunodeficiency virus and acquired immunodeficiency syndrome(PLWHA)who failed anti-retroviral therapy(ART)in Henan Province,in order to provide a basis for adjusting ART regimens and reducing drug resistance.Methods PLWHA with virological failure(human immunodeficiency virus(HIV)RNA≥500 copies/mL)after receiving ART for more than 24 weeks were included in Henan Province from January 2018 to December 2022.Baseline CD4+T lymphocyte counts,ART regimens and other clinical data were collected.HIV-1 gene subtypes and their drug resistance sequence mutations were detected in the Sixth People′s Hospital of Zhengzhou,and the sequences were submitted to the HIV Drug Resistance Interpretation System of Stanford University for comparison of test results.Genotypic drug resistance to nucleotide reverse transcriptase inhibitors(NRTI),non-nucleoside reverse transcriptase inhibitors(NNRTI),protease inhibitors(PI)and integrase inhibitors(INSTI)was determined.Multivariate logistic regression was used to analyze the influencing factors of drug resistance in patients with ART failure.Results Among 982 PLWHA,the sequences of 899 cases were successfully amplified,and drug resistance was detected in 737 cases,with the drug resistance rate of 81.98%(737/899).The rates of resistance to NRTIs,NNRTIs,PIs and INSTIs were 71.97%(647/899),79.31%(713/899),5.23%(47/899)and 2.72%(20/734),respectively.The largest number of those who developed concomitant resistance to two classes of drugs was 588 cases(79.78%),mainly NRTI and NNRTI concomitant resistance in 583 cases(79.10%).There were 99 cases(13.43%)who developed resistance to only one class of drugs,and those who developed concurrent resistance to three classes of drugs were 48 cases(6.51%),and two cases(0.27%)were found to be resistant to all four classes of drugs mentioned above.A total of 10 HIV genotypes were detected,among which subtype B accounted for the most(59.73%(537/89

关 键 词：人类免疫缺陷病毒感染 获得性免疫缺陷综合征 抗逆转录病毒治疗 基因型耐药 影响因素 

分 类 号：R512.91[医药卫生—内科学]