TDF 的累积暴露与肾小管病有关，无论其目前是否正在使用或已停用。

Cumulative exposure of TDF is associated with kidney tubulopathy whether it is currently used or discontinued.

机构信息

AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo.

Department of Drug Evaluation and Informatics, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.

出版信息

AIDS. 2018 Jan 14;32(2):179-188. doi: 10.1097/QAD.0000000000001667.

DOI:10.1097/QAD.0000000000001667

PMID:29028660

Abstract

OBJECTIVE

Tenofovir disoproxil fumarate (TDF) increases the risk of kidney tubular dysfunction (KTD). This study was conducted to elucidate whether KTD persists after discontinuation of TDF.

DESIGN

A prospective cross-sectional study which enrolled 941 HIV-1-infected patients.

METHODS

KTD was predefined as the presence of at least two abnormalities among the five tubular markers (fractional excretion of phosphate, fractional excretion of uric acid, β2 microglobulinuria, N-acetyl-β-D-glucosaminidase, nondiabetic glycosuria). Logistic regression model was used to examine the association between KTD and cumulative TDF use, as well as current status of TDF use.

RESULTS

In total, 94% of study patients were men (median age 45, estimated glomerular filtration rate 75 ml/min per 1.73 m, CD4 575 cells/μl. About 98% were on antiretroviral therapy. In total, 64% of the patients ever used TDF and 39% currently used TDF. Twenty-nine percent used TDF for more than 5 years. KTD was diagnosed in 116 (12%) patients. In multivariate model, more than 5 years of TDF exposure and current TDF use [odds ratio (OR) 4.2, 95% confidence interval (CI) 2.37-7.56], more than 5 years and past TDF use (OR 2.4, 95% CI 1.09-5.33), less than 5 years and current TDF (OR 2.4, 95% CI 1.24-4.85), and less than 5 years and past TDF (OR 2.4, 95% CI 1.22-4.64) were all significantly associated with KTD, with never TDF use as reference. The results were the same using 4 and 3 years of exposure as the cutoff. However, with 2 years exposure, both less than 2 years and current TDF (OR 2.3, 95% CI 0.84-6.20) and less than 2 years and past TDF (OR 1.9, 95% CI 0.73-4.93) were not associated with KTD, whereas both more than 2 years and current TDF and more than 2 years and past TDF were associated.

CONCLUSION

The association between cumulative TDF use and KTD was strong and robust. The results of the study suggested that TDF-related KTD might persist after discontinuation of TDF if patients used TDF for more than 2 years.

摘要

目的

富马酸替诺福韦二吡呋酯（TDF）会增加肾小管功能障碍（KTD）的风险。本研究旨在阐明 TDF 停药后 KTD 是否持续存在。

设计

一项前瞻性的横断面研究，共纳入 941 名 HIV-1 感染患者。

方法

将至少有 5 种肾小管标志物（磷排泄分数、尿酸排泄分数、β2 微球蛋白尿、N-乙酰-β-D-氨基葡萄糖苷酶、非糖尿病性糖尿）中两种以上异常定义为 KTD。使用逻辑回归模型来检查 KTD 与累积 TDF 使用、以及当前 TDF 使用之间的关系。

结果

研究中，94%的患者为男性（中位年龄 45 岁，估计肾小球滤过率 75ml/min/1.73m2，CD4 575 个/μl。约 98%的患者正在接受抗逆转录病毒治疗。共有 64%的患者曾经使用过 TDF，39%的患者目前正在使用 TDF。29%的患者使用 TDF 超过 5 年。116 名（12%）患者被诊断为 KTD。在多变量模型中，超过 5 年的 TDF 暴露和当前 TDF 使用[比值比（OR）4.2，95%置信区间（CI）2.37-7.56]、超过 5 年且过去使用过 TDF（OR 2.4，95%CI 1.09-5.33）、使用 TDF 不足 5 年且当前使用（OR 2.4，95%CI 1.24-4.85）和使用 TDF 不足 5 年且过去使用过（OR 2.4，95%CI 1.22-4.64）均与 KTD 显著相关，从未使用过 TDF 作为参考。使用 4 年和 3 年的暴露作为截定点，结果相同。然而，暴露时间不足 2 年且当前使用 TDF（OR 2.3，95%CI 0.84-6.20）和暴露时间不足 2 年且过去使用过 TDF（OR 1.9，95%CI 0.73-4.93）与 KTD 无关，而暴露时间超过 2 年且当前使用 TDF 和暴露时间超过 2 年且过去使用过 TDF 与 KTD 相关。