人类免疫缺陷病毒感染/艾滋病经治患者转换多替拉韦联合拉米夫定简化治疗方案的疗效与耐受性分析

Efficacy and tolerability of dolutegravir plus lamivudine as a switch simplified strategy in treatment-experienced human immunodeficiency virus/acquired immunodeficiency syndrome patients

目的评估人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染/艾滋病经治患者转换为多替拉韦联合拉米夫定二联治疗方案后的疗效和耐受性。方法纳入2016年9月至2019年5月就诊于首都医科大学附属北京佑安医院因各种原因改用多替拉韦(50 mg,1次/d)+拉米夫定(300 mg,1次/d)二联治疗方案的HIV感染/艾滋病经治患者,收集患者改变治疗方案时(基线)和转换治疗48周后的HIV RNA、CD4^(+)T淋巴细胞计数、血脂指标、肾功能指标,分析二联方案的有效性(HIV RNA<50拷贝/mL)和安全性。统计学比较采用威尔科克森配对符号秩检验。结果33例HIV感染/艾滋病经治患者中,改变治疗方案的原因分别为病毒学失败[12.1%(4/33)]、简化治疗方案[33.3%(11/33)]和发生药物毒性反应[54.5%(18/33)]。转换治疗方案前接受抗反转录病毒治疗时长为2.13(1.05,4.23)年,29例(87.9%)患者在改变治疗方案时处于病毒学抑制状态,4例(12.1%)病毒学失败。转换治疗48周后,33例患者HIV RNA均<50拷贝/mL。基线CD4^(+)T淋巴细胞计数为543(363,595)/μL,转换治疗48周后升高至625(455,651)/μL,差异有统计学意义(Z=3.14,P=0.002)。与基线水平比较,转换治疗48周后低密度脂蛋白胆固醇升高[2.35(1.80,3.08)mmol/L比3.12(2.74,3.87)mmol/L],而三酰甘油[2.21(1.27,4.37)mmol/L比1.61(1.20,2.22)mmol/L]、总胆固醇与高密度脂蛋白胆固醇比值[5.02(4.13,6.40)比4.70(3.55,5.35)]和估算肾小球滤过率水平[106.4(78.2,118.2)mL/(min·1.73 m^(2))比88.6(75.7,107.9)mL/(min·1.73 m^(2))]均降低,差异均有统计学意义(Z=4.89、2.37、2.09、2.83,均P<0.050)。随访过程中无患者因不良反应停药。结论对先前接受过其他治疗方案的HIV感染/艾滋病经治患者使用多替拉韦联合拉米夫定的二联方案是有效的,且耐受性良好,没有明显不良反应。

Objective To evaluate the efficacy and tolerability of the dual therapy of dolutegravir(DTG)plus lamivudine(3TC)as a switch simplified strategy in treatment-experienced human immunodeficiency virus(HIV)/acquired immunodeficiency syndrome(AIDS)patients.Methods Treatment-experienced HIV/AIDS patients who switched to a dual therapy containing DTG(50 mg,once daily)plus 3TC(300 mg,once daily)were included in Beijing You′an Hospital,Capital Medical University from September 2016 to May 2019.HIV RNA,CD4^(+)T lymphocyte count,blood lipid indexes,renal function indexes were collected when patients changed the treatment regimen(baseline)and after 48 weeks of treatment.Efficacy(HIV RNA<50 copies/mL)and safety of the dual therapy were analyzed.Statistical comparisons were performed using the Wilcoxon matched-pairs signed rank test.Results The reasons for 33 patients switching the treatment regimen were virologic failure(four cases,12.1%),simplification of regimen(11 cases,33.3%),and drug toxicity(18 cases,54.5%).The patients were treated with anti-retroviral therapy(ART)for 2.13(1.05,4.23)years before regimens switching.Twenty-nine(87.9%)patients were virologically suppressed at baseline,and four(12.1%)patients were virological failure.After switching to DTG plus 3TC,all 33 patients showed HIV RNA<50 copies/mL after 48 weeks of treatment.The baseline CD4^(+)T lymphocyte count was 543(363,595)/μL.After switching the treatment regimens for 48 weeks,CD4^(+)T lymphocyte count was significantly increased to 625(455,651)/μL,and the difference was statistically significant(Z=3.14,P=0.002).Compared with baseline,low-density lipoprotein-cholesterol was increased after 48 weeks of treatment(2.35(1.80,3.08)mmol/L vs 3.12(2.74,3.87)mmol/L),while triglyceride(2.21(1.27,4.37)mmol/L vs 1.61(1.20,2.22)mmol/L),the ratio of total cholesterol to high-density lipoprotein-cholesterol(5.02(4.13,6.40)vs 4.70(3.55,5.35))and estimated glomerular filtration rate(106.4(78.2,118.2)mL/(min·1.73 m^(2))vs 88.6(75.7,107.9)mL/(min·1.73 m^(2)))were decreased.The differences were all statistically significant(Z=4.89,2.37,2.09 and 2.83,respectively,all P<0.050).No patient discontinued due to adverse events.Conclusions The use of dual therapy containing DTG and 3TC is effective and well-tolerated in treatment-experienced HIV/AIDS patients under any prior ART without significant adverse events.