河南省1922例艾滋病一线抗病毒治疗失败患者中HIV耐药基因突变情况分析

Analysis of HIV-1 drug resistance among 1 922 individuals experiencing virological failure of first-line antiretroviral therapy in Henan province

目的分析河南省艾滋病一线抗病毒治疗失败患者中HIV耐药基因突变发生情况。方法利用中国法定传染病监测信息网络直报系统子平台——艾滋病综合防治数据信息管理系统，收集2011年河南省9个地级市中接受一线艾滋病抗病毒治疗〉1年，病毒载量〉1000拷贝／ml的患者的基本信息。删除基本信息缺失（40例）、病例以及耐药检测结果不完整（212例）者，共计1922例艾滋病患者纳入本研究，并对其进行基因型耐药检测。采用多因素非条件logistic回归模型分析含HIV耐药毒株的艾滋病患者发生基因突变的影响因素。结果1922例发生一线抗病毒治疗失败的艾滋病患者中，男性1039例，女性833例，年龄为（45．7±12．1）岁，已婚者占82．73％（1590例），感染途径多为血液传播，占87．93％（1690例）。64．20％（1234例）的患者存在有效的耐药基因突变，核苷类逆转录酶抑制剂（NRTI）、非核苷类逆转录酶抑制剂（NNRTI）和蛋白酶抑制剂（PI）类药物耐药基因突变的发生率分别为62．59％（1203例），49．74％（956例）和0．94％（18例），同时发生NRTI和NNRTI耐药突变的患者占42．09％（809例）。~ITAM是发生率较高的NRTI耐药基因突变位点，占41．94％（806例），TAM-1和TAM-2的发生率分别是8．48％（163例）和4．24％（81例）。存在K65R／N和Q151M耐药突变复合体患者分别为23和4例。K103N／S是发生率较高的NNRTI耐药基因突变位点，占34．32％（659例）。多因素非条件logistic回归模型分析显示，母婴传播（OR=9．05，95％C1：1．14～72．12）、临床分期为Ⅳ期（OR=I．70，95％CI：1．09～2．66）和治疗5年（OR=I．59，95％CI：1．03—2．47）的患者耐药发生率高；治疗1年（OR=O．19，95％CI：0．13～0．27）的患者耐药发生率低。结论河南省一线抗病毒治疗失败患者的耐药突变多样，模式较复杂，母婴传播、临床分期为Ⅳ期及治疗5年的患者发生耐药基因突变的风险高。

Objective To study the condition of HIV-1 drug resistance mutation among failures of first-fine antiretroviral therapy in Henan province. Method The sub platform of China＇s legal infectious disease monitoring information reporting system-HIV/AIDS integrated prevention and control data information management system was used to collect the information of patients experiencing first-line antiretroviral treatment failure （virus load≥1 000 copies/ml） more than one year among nine cities of Henan in 2011.A total of 40 cases with no information and 212 cases with incomplete drug resistance results were deleted, and 1 922 cases were included in this study and genotype resistance testing was carried out. Non-conditional logistic regression analysis was used to analyse the influencing factors of drug resistance mutation. Results A total of 1 922 cases were included in the analysis. 1 039 cases were males, 833 cases were females, the age was （45.7 ± 12.1） years, 82.73% （1 590） were married, and 87.93%（1 690） were transmitted by blood. 64.20% （1 234） patients acquired drug resistance. Nucleoside reverse transcriptase inhibitor （NRTI）, non-nucleoside reverse transcriptase inhibitor （NNRTI） and protease inhibitor （PI） resistanee mutations were found in 62.59% （1 203）, 49.74% （956） and 0.94% （18） of subjects, respectively. 42.09% （809） of patients harbored NRTI and NNRTI resistanee mutations synchronously. ≥ITAM was the most commonly emerged NRTI resistance mutation （41.94% （806））, the prevalences of TAM-1 and TAM-2 were 8.48% （163） and 4.24% （81）, respectively. K65R/N and Q151M complex existed in 23 and 4 patients, respectively. K103N/S was the most commonly emerged NNRTI resistance mutation （34.32% （659））. Non-conditional logistic regression analysis showed that, faetors associated with high drug resistance were the following： transmitted by mother to child （0R=9.05,95%CI： 1.14-72.12）, clinical stage was IV （OR=1.70, 95% CI： 1.09-2.66） and 5-year-treated （OR=1.59,95% CI： 1.03-2.47）. Factors associated with low drug resistance were the following： 1-year-treated （OR=0.19, 95%CI：0.13-0.27）. Conclusion Complex patterns of HIV-1 drug resistance mutations were identified among individuals experieneing failure of first-line antiretroviral therapy in Henan province. Factors associated with high drug resistanee were lived in Luohe, Shangqiu, Nanyang, Xinyang, transmitted by mother to child, clinical stage was IV, and 5-year-treated.