Goicoechea Miguel, Liu Shanshan, Best Brookie, Sun Shelly, Jain Sonia, Kemper Carol, Witt Mallory, Diamond Catherine, Haubrich Richard, Louie Stan
Antiviral Research Center, University of California, San Diego, 150 W. Washington St., Ste. 100, San Diego, CA 92103, USA.
J Infect Dis. 2008 Jan 1;197(1):102-8. doi: 10.1086/524061.
Plasma concentrations of tenofovir increase when the drug is coadministered with some ritonavir-boosted protease inhibitors (PI/r). We hypothesized that tenofovir disoproxil fumarate (TDF)-treated patients taking PI/r-based regimens would have a greater decline in renal function than patients receiving nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based therapy.
We compared the estimated decline in renal function among 146 human immunodeficiency virus type 1 (HIV-1)-infected patients receiving a TDF+PI/r- (n = 51), TDF+NNRTI- (n = 29), or non-TDF-containing (n = 66) regimen. Plasma tenofovir concentrations were measured at study week 2, and rates of creatinine clearance (CrCl) were estimated using the Cockcroft-Gault (C-G) and Modification of Diet in Renal Disease (MDRD) equations. Mixed-effects models were used to analyze regimen type and tenofovir concentration as predictors of change in CrCl from baseline to weeks 24 and 48.
Decreases in C-G estimates of CrCl were not significantly different among the 3 groups during the first 24 weeks of therapy. However, in adjusted analyses, patients receiving TDF+PI/r had a greater rate of decline in CrCl than did the TDF+NNRTI group (for C-G, -13.9 vs. -6.2 mL/min/year [P = .03]; for MDRD, -14.7 vs. -4.5 mL/min/1.73 m(2)/year [P = .02]). Among TDF-treated patients, tenofovir plasma concentration was not associated with CrCl over time.
Treatment with TDF and PI/r was associated with greater declines in renal function over 48 weeks compared with TDF+NNRTI-based regimens.
当替诺福韦与某些利托那韦增强的蛋白酶抑制剂（PI/r）合用时，其血浆浓度会升高。我们推测，接受基于PI/r方案治疗的富马酸替诺福韦二吡呋酯（TDF）患者，其肾功能下降幅度会大于接受基于非核苷类逆转录酶抑制剂（NNRTI）治疗的患者。
我们比较了146例1型人类免疫缺陷病毒（HIV-1）感染患者的肾功能估计下降情况，这些患者分别接受TDF+PI/r方案（n = 51）、TDF+NNRTI方案（n = 29）或不含TDF的方案（n = 66）。在研究第2周时测量血浆替诺福韦浓度，并使用Cockcroft-Gault（C-G）和肾脏病饮食改良（MDRD）方程估算肌酐清除率（CrCl）。采用混合效应模型分析方案类型和替诺福韦浓度，作为从基线到第24周和48周CrCl变化的预测因素。
在治疗的前24周，3组患者C-G估算的CrCl下降情况无显著差异。然而，在调整分析中，接受TDF+PI/r的患者CrCl下降速率高于TDF+NNRTI组（C-G法，-13.9 vs. -6.2 mL/min/年 [P = .03]；MDRD法，-14.7 vs. -4.5 mL/min/1.73 m²/年 [P = .02]）。在接受TDF治疗的患者中，替诺福韦血浆浓度与CrCl随时间的变化无关。
与基于TDF+NNRTI的方案相比，TDF与PI/r联合治疗在48周内肾功能下降幅度更大。
