Casado J L, Santiuste C, Vivancos M J, Monsalvo M, Moreno A, Perez-Elías M J, Del Rey J M, Moreno S
Department of Infectious Diseases and Biochemistry, Ramon y Cajal Hospital, Madrid, Spain.
HIV Med. 2018 Jun 22. doi: 10.1111/hiv.12630.
We investigated the reversibility of tenofovir disoproxil fumarate (TDF)-associated renal decline and tubular dysfunction using different antiretroviral strategies.
A successive evaluation of renal [estimated glomerular filtration rate (eGFR)] and tubular (phosphataemia, proteinuria, albuminuria, phosphaturia, uricosuria, glycosuria and tubular proteinuria) parameters was performed in 231 patients, before and after switching from TDF to abacavir (n = 60), using dual therapy (n = 49), or continuing the same regimen including TDF (n = 122).
In a successive evaluation after a median of 8.86 months, or less time if treatment was switched (4.8 months vs. 13.3 months to second evaluation; P < 0.01), a significant improvement in eGFR (median change +0.3 vs. -2.91 mL/min/1.73 m in patients who did not discontinue TDF; P = 0.04) and tubular dysfunction (median change -40% vs. +30%, respectively; P < 0.01) was observed. Lineal regression showed that age (β = -0.14; P = 0.04), previous eGFR decline (β = -0.42; P < 0.01), and time on TDF (β = -0.19; P = 0.04) were associated with impaired eGFR recovery. There were no differences in eGFR slopes between patients using abacavir instead of TDF and those using a dual therapy, who showed similar improvement in proteinuria (-22% vs. -19%, respectively), phosphaturia (+10.1% vs. +9.4%, respectively), and urinary beta-2-microglobulin (-9% vs. -15%, respectively; P > 0.1 for all), although patients receiving the dual regimen were more heavily pretreated. A eGFR decrease (-6.17 mL/min/1.73 m ) was observed in patients taking dolutegravir or rilpivirine, but with similar improvement to that observed in the rest of switching patients in tubular abnormalities.
Tenofovir disoproxil fumarate discontinuation was associated with a rapid and significant improvement in eGFR and tubular abnormalities, regardless of whether abacavir or dual therapy was chosen. Switching to a regimen that included dolutegravir and/or rilpivirine was associated with a eGFR decrease without differences in the rate of tubular dysfunction improvement in comparison with the rest of patients who discontinued tenofovir.
我们使用不同的抗逆转录病毒策略研究了富马酸替诺福韦二吡呋酯（TDF）相关的肾功能下降和肾小管功能障碍的可逆性。
对231例患者在从TDF转换为阿巴卡韦（n = 60）、使用联合治疗（n = 49）或继续使用含TDF的相同方案（n = 122）之前和之后，进行了肾脏[估计肾小球滤过率（eGFR）]和肾小管（血磷、蛋白尿、白蛋白尿、磷尿、尿酸尿、糖尿和肾小管蛋白尿）参数的连续评估。
在中位时间8.86个月后的连续评估中，或如果进行了治疗转换则时间更短（第二次评估为4.8个月对13.3个月；P < 0.01），观察到eGFR有显著改善（未停用TDF的患者中位变化为 +0.3对 -2.91 mL/min/1.73 m²；P = 0.04）和肾小管功能障碍（中位变化分别为 -40%对 +30%；P < 0.01）。线性回归显示年龄（β = -0.14；P = 0.04）、先前的eGFR下降（β = -0.42；P < 0.01）和使用TDF的时间（β = -0.19；P = 0.04）与eGFR恢复受损相关。使用阿巴卡韦替代TDF的患者与使用联合治疗的患者之间的eGFR斜率没有差异，他们在蛋白尿（分别为 -22%对 -19%）、磷尿（分别为 +10.1%对 +9.4%）和尿β2微球蛋白（分别为 -9%对 -15%；所有P > 0.1）方面显示出相似的改善，尽管接受联合方案的患者预处理更重。服用多替拉韦或利匹韦林的患者观察到eGFR下降（-6.17 mL/min/1.73 m²），但在肾小管异常方面与其他转换患者的改善相似。
无论选择阿巴卡韦还是联合治疗，停用富马酸替诺福韦二吡呋酯均与eGFR和肾小管异常的快速且显著改善相关。转换为包含多替拉韦和/或利匹韦林的方案与eGFR下降相关，与停用替诺福韦的其他患者相比，肾小管功能障碍改善率无差异。
