Gianotti Nicola, Galli Laura, Poli Andrea, Salpietro Stefania, Nozza Silvia, Carbone Alessia, Merli Marco, Ripa Marco, Lazzarin Adriano, Castagna Antonella
From the Infectious Diseases (NG, LG, AP, SS, SN, AC, MM, MR, AL, AC), San Raffaele Scientific Institute; and Università Vita-Salute San Raffaele (AP, AC, MM, MR, AL, AC), Milano, Italy.
Medicine (Baltimore). 2016 May;95(22):e3780. doi: 10.1097/MD.0000000000003780.
The aim of the study was to evaluate in human immunodeficiency virus (HIV)-infected patients estimated glomerular filtration rate (eGFR) trajectories during treatment with different protease inhibitors (PIs) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus tenofovir (TDF) or abacavir (ABC) and lamivudine or emtricitabine (xTC).Retrospective study of patients followed at a single clinical center; all patients who started TDF or ABC for the first time with a NNRTI or lopinavir/r (LPV/r) or atazanavir/r (ATV/r) or darunavir/r (DRV/r), for whom at least 1 eGFR value before the start and during the studied treatment was known, were included in this analysis. eGFR was calculated by means of the CKD-EPI formula. Univariate and multivariate mixed linear model (MLM) was applied to estimate eGFR slope with the considered antiretroviral treatment.In the 1658 patients treated with TDF/xTC (aged 43 [37-48] years, with an eGFR of 105 [96; 113] mL/min/1.73 m, 80% males, 92% Caucasians, 10% coinfected with HCV, 4% with diabetes, 11% with hypertension, 38% naive for antiretroviral therapy (ART), 37% with HIV-RNA <50 copies/mL) the median follow-up was 2.5 (1.2-4.6) years. Their adjusted eGFR slopes (95% CI) were -1.26 (-1.58; -0.95), -0.43 (-1.20; +0.33), -0.86 (-1.28; -0.44), and -0.20 (-0.42; +0.02) mL/min/1.73 m per year in patients treated with ATV/r, DRV/r, LPV/r, and NNRTI, respectively. Patients receiving ATV/r or LPV/r had a greater adjusted decline in eGFR compared with those receiving NNRTIs (difference -1.06 [-1.44; -0.69] mL/min/1.73 m per year, P <0.001; and -0.66 [-1.13; -0.20] mL/min/1.73 m per year, P = 0.005, respectively); adjusted eGFR slopes were similar in patients receiving DRV/r and in those receiving NNRTIs. Patients receiving ATV/r had a greater adjusted eGFR decline than those treated with DRV/r (difference -0.83 [-1.65; -0.02] mL/min/1.73 m per year; P = 0.04), but not than those receiving LPV/r; no significant difference was observed in adjusted eGFR slopes between patients receiving DRV/r and those receiving LPV/r. In the 286 patients treated with ABC and lamivudine, eGFR slopes were similar, independent of the PI.In patients receiving TDF/xTC, eGFR trajectories were small for all regimens and declined less in patients receiving DRV/r or NNRTIs than in those treated with ATV/r or LPV/r.
本研究旨在评估人类免疫缺陷病毒(HIV)感染患者在接受不同蛋白酶抑制剂(PI)或非核苷类逆转录酶抑制剂(NNRTI)加替诺福韦(TDF)或阿巴卡韦(ABC)及拉米夫定或恩曲他滨(xTC)治疗期间的估计肾小球滤过率(eGFR)轨迹。对在单一临床中心接受随访的患者进行回顾性研究;纳入所有首次开始使用TDF或ABC联合NNRTI或洛匹那韦/利托那韦(LPV/r)或阿扎那韦/利托那韦(ATV/r)或达芦那韦/利托那韦(DRV/r)治疗且在开始治疗前及研究治疗期间至少有1个eGFR值的患者进行分析。eGFR通过CKD-EPI公式计算。应用单变量和多变量混合线性模型(MLM)来估计所考虑的抗逆转录病毒治疗的eGFR斜率。在1658例接受TDF/xTC治疗的患者中(年龄43[37 - 48]岁,eGFR为105[96;113]mL/min/1.73m²,80%为男性,92%为白种人,10%合并丙型肝炎病毒感染,4%患有糖尿病,11%患有高血压,38%为抗逆转录病毒治疗(ART)初治患者,37%的HIV-RNA<50拷贝/mL),中位随访时间为2.5(1.2 - 4.6)年。接受ATV/r、DRV/r、LPV/r和NNRTI治疗的患者其调整后的eGFR斜率(95%CI)分别为每年-1.26(-1.58;-0.95)、-0.43(-1.20;+0.33)、-0.86(-1.28;-0.44)和-0.20(-0.42;+0.02)mL/min/1.73m²。与接受NNRTIs治疗的患者相比,接受ATV/r或LPV/r治疗的患者eGFR调整后的下降幅度更大(差异分别为每年-1.06[-1.44;-0.69]mL/min/1.73m²,P<0.001;以及每年-0.66[-1.13;-0.20]mL/min/1.73m²,P = 0.005);接受DRV/r治疗的患者与接受NNRTIs治疗的患者调整后的eGFR斜率相似。接受ATV/r治疗的患者eGFR调整后的下降幅度比接受DRV/r治疗的患者更大(差异为每年-0.83[-1.65;-0.02]mL/min/1.73m²;P = 0.04),但不比接受LPV/r治疗的患者大;接受DRV/r治疗的患者与接受LPV/r治疗的患者调整后的eGFR斜率之间未观察到显著差异。在2