2011—2019年云南省死亡HIV感染者/AIDS患者获得性耐药调查  

Analysis on the acquired drug resistance of deceased HIV/AIDS patients in Yunnan

作　　者：李健健 张桂仙 邱钰婷 周熙姝 刘家法 劳云飞 楼金成 张米 董兴齐 LI Jian-jian;ZHANG Gui-xian;QIU Yu-ting;ZHOU Xi-shu;LIU Jia-fa;LAO Yun-fei;LOU Jin-cheng;ZHANG Mi;DONG Xing-qi(Yunnan Infectious Diseases Hospital/AIDS Care Center,Kunming,Yumman 650301,China;不详)

机构地区：[1]云南省传染病医院艾滋病关爱中心,云南昆明650301 [2]昆明医科大学公共卫生学院

出　　处：《中国预防医学杂志》2022年第4期241-249,共9页Chinese Preventive Medicine

基　　金：国家自然科学基金地区基金(81960605);云南省高层次卫生技术人才培养经费资助项目(H-2018050);云南省艾滋病病毒学及临床诊疗技术创新研究中心(202102AA310005)。

摘　　要：目的调查2011—2019年云南省接受抗病毒治疗后死亡的人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染者和获得性免疫缺陷综合征(acquired immunodeficiency syndrome,AIDS)患者基因型耐药率、耐药程度、突变位点分布及其与非死亡患者的耐药差异。方法采用横断面研究方法,收集患者耐药相关流行病学信息。通过In house方法,运用逆转录巢式聚合酶链式反应(reverse transcription nested polymerase chain reaction,RT-nested-PCR)扩增患者HIV-1 pol基因序列,测序后进行比对分析,阐明两组患者耐药率及三类抗病毒药物耐药情况。结果纳入HIV/AIDS相关致死亡患者415例,扩增阳性样本345例,发生耐药突变221例(64.06%),在抗病毒治疗失败的死亡患者中耐药率较非死亡患者73.48%(169/230)低,粗略估计HIV-1在死亡人群中总体耐药率为1.51%(221/14603)。死亡患者耐药发生的影响因素包括性别、年龄、感染途径、初始CD4~+T淋巴细胞计数和治疗方案(χ^(2)=23.603、15.558、9.856、27.871、37.017,P均<0.05),死亡患者核苷类抑制剂(nucleoside reverse transcriptase inhibitors,NRTIs)、非核苷类抑制剂(non-nucleoside reverse transcriptase inhibitors,NNRTIs)以及蛋白酶抑制剂(protease inhibitors,PIs)的耐药率分别为64.25%(142/221)、85.52%(189/221)、4.98%(11/221);三类药物出现频率最高的突变位点依次为NRTIs-M184V/I(59.28%),NNRTIs-K103N/S(28.74%),PIs-L23I(1.37%)。结论云南省死亡HIV感染者/AIDS患者三类抗病毒药物耐药率与非死亡组患者略有差异。应加强对HIV感染者/AIDS患者危重症患者治疗的管理和基因型耐药的检测,控制耐药毒株的产生,进一步降低患者死亡率。Objective To analyze the mechanism of acquired drug resistance of deceased HIV/AIDS patients who received anti-viral treatment in Yunnan from 2011 to 2019.Methods A cross-sectional study was performed to collect epidemiological information related to drug resistance of HIV/AIDS patients.Using the in house method,HIV-1 pol gene was amplified by RT-PCR,and the sequences were analyzed and compared between deceased and non-deceased patients and among patients treated with 3 types of antiviral drugs.Results A total of 415 deceased HIV/AIDS patients were included in the study.345 were positive for RT-PCR,and drug-resistant mutations were found in 221 cases(64.06%).The drug-resistant rate was 73.48%(169/230)in non-deceased patients which was higher than that in deceased patients.A rough estimated overall drug resistant rate of HIV-1 in deceased cases was 1.51%(221/14603).The influencing factors for drug resistance in deceased patients included gender,age,infection routes,initial CD4+cell counts and treatment plan(χ^(2)=23.603,15.558,9.856,27.871,37.017,P<0.05).The drug resistance rates to nucleoside inhibitors(NRTIs),non-nucleoside inhibitors(NNRTIs)and protease among deceased patients were 64.25%(142/221),85.52%(189/221)and 4.98%(11/221),respectively.The most common mutation sites was NRTIs-M184V(59.28%),followed by NNRTIs-K103N/S(28.74%)and PIs-L23I(1.37%).Conclusions There is a slight difference in the resistance rates to three types HAART drugs between deceased HIV/AIDS patients and non-deceased patients in Yunnan.We should strengthen the management of antiviral treatment and genotyping resistance testing in critically illed HIV/AIDS patients,control the emergence of drug-resistant strains,and further reduce the mortality of HIV/AIDS patients.

关 键 词：人类免疫缺陷病毒 高效联合抗逆转录病毒治疗 死亡患者 获得性耐药 

分 类 号：R512.9[医药卫生—内科学]