四川省部分地区HIV-1感染者二线方案抗病毒治疗效果及耐药突变分析  

The antiretroviral treatment effect and drug resistance mutation of antiretroviral treatment for HIV-1 infected patients using second-line regimen in some areas of Sichuan Province

作　　者：袁丹[1] 李一平 杨淑娟[2] 刘芳[3] 黄晓玲[4] 姚亮 李玲 周玚 叶黎[1] 曾亚莉[1] 梁姝[1] Yuan Dan;Li Yiping;Yang Shujuan;Liu Fang;Huang Xiaoling;Yao Liang;Li Ling;Zhou Chang;Ye Li;Zeng Yali;Liang Shu(Center for AIDS/STD Control and Prevention,Sichuan Provincial Center for Disease Control and Prevention,Chengdu 610044,China;West China School of Public Health and West China Fourth Hospital,Sichuan University,Chengdu 610044,China;Chengdu Center for Disease Control and Prevention,Chengdu 610041,China;Yibin Center for Disease Control and Prevention,Yibin 644002,China;Butuo County People's Hospital,Butuo 616350,China)

机构地区：[1]四川省疾病预防控制中心性病艾滋病预防控制所,成都610044 [2]四川大学华西公共卫生学院,成都610044 [3]成都市疾病预防控制中心,成都610041 [4]宜宾市疾病预防控制中心,宜宾644002 [5]布拖县人民医院,布拖616350

出　　处：《中华流行病学杂志》2023年第2期276-284,共9页Chinese Journal of Epidemiology

基　　金：四川省卫生与健康委员会科研课题(20PJ121);四川省科学技术厅科研课题(2020YJ0449);国家科技重大专项(2017ZX10201101)。

摘　　要：目的分析四川省部分地区接受一线方案并发生耐药的HIV-1感染者更换二线方案后抗病毒治疗(ART)效果及耐药突变。方法采用队列研究方法,2019年1月1日至2021年12月31日对接受一线方案发生耐药的HIV-1感染者随访2年,采用χ^(2)检验分析观察终点CD4+T淋巴细胞(CD4)计数、病毒载量(VL)变化及耐药突变情况的差异,使用多因素logistic回归模型分析更换二线方案且依从性较好的HIV-1感染者ART效果的影响因素。结果共招募HIV-1感染者737例,在持续保持较好依从性的情况下,及时更换二线方案HIV-1感染者持续CD4计数>200个/μl和持续病毒抑制的比例较高(P<0.05),其中基线不同耐药程度HIV-1感染者持续CD4计数>200个/μl和持续VL<200拷贝数/ml(持续病毒抑制)的比例差异无统计学意义(P>0.05)。更换二线方案后,部分蛋白酶抑制剂和非核苷类反转录酶抑制剂的耐药突变位点分别呈上升和下降趋势(P<0.05)。多因素logistic回归分析结果显示,在更换二线方案且依从性较好的HIV-1感染者中,未持续病毒抑制的影响因素包括母婴传播是异性性传播感染的3.01(95%CI:1.29~7.00)倍、未及时更换二线方案是及时更换二线方案的2.55(95%CI:1.41~4.62)倍、CRF85_BC亚型是CRF01_AE亚型的3.32(95%CI:1.49~7.42)倍。结论一线方案耐药差异不影响更换二线方案后的四川省HIV-1感染者ART效果;及时更换二线方案并保持良好依从性,有助于提高HIV-1感染者免疫水平和持续保持较低VL水平。母婴传播、未及时更换二线方案和感染CRF85_BC亚型是HIV-1感染者更换二线方案后影响ART成功的危险因素。Objective To analyze the treatment effect and drug resistance mutation of HIV-1 infected patients who changed to the second-line antiretroviral treatment regimen after they had developed drug-resistance with first-line antiretroviral treatment regimen in some areas of Sichuan Province.Methods Using the cohort study method,the patients who had developed drug resistance with the first-line regimen were followed up for two years from 1 January 2019 to 31 December 2021.The changes of CD4+T lymphocytes(CD4)counts and viral load(VL)at the endline and the detection of drug-resistant mutation sites were analyzed using the chi-square test.Multivariate logistic regression model was used to analyze the influencing factors of antiretroviral treatment effect in patients who had good compliance after switching to the second-line regimen.Results A total of 737 patients were recruited.Among the cases with continuous good compliance,those who timely changed to the second-line regimen had higher proportion of maintaining continuous CD4>200 cells/μl and sustained virus inhibition(P<0.05).Among the patients with different levels of drug resistance at baseline,there was no significant difference in continuous CD4>200 cells/μl and sustained VL<200 copies/ml(P>0.05).After changing to the second-line regimen,the drug-resistant mutation sites of some protease inhibitors showed an upward trend,while those of the non-nucleoside reverse transcriptase inhibitors showed a downward trend(P<0.05).Multivariate logistic regression analysis showed that,among patients who had good compliance and who had switched to the second-line regimen,mother-to-child-transmitted patients had 3.01 times higher risk than heterosexual sexually transmitted infection(95%CI:1.29-7.00),failure to change the second-line protocol in time brought 2.55 times higher risk than that of timely changing to the second-line regimen(95%CI:1.41-4.62)and patients who infected with CRF85_BC subtype had 3.32 times higher risk than those infected with CRF01_AE subtype(95%CI:1.49-7.4

关 键 词：艾滋病病毒 抗病毒治疗 二线方案 耐药突变 

分 类 号：R512.91[医药卫生—内科学]