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在真实环境中,将富马酸替诺福韦二吡呋酯转换为替诺福韦艾拉酚胺:会有哪些影响?

Switching tenofovir disoproxil fumarate to tenofovir alafenamide in a real life setting: what are the implications?

机构信息

Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.

German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany.

出版信息

HIV Med. 2020 Jul;21(6):378-385. doi: 10.1111/hiv.12840. Epub 2020 Feb 17.

Abstract

OBJECTIVES

Development of novel antiretrovirals aims at reducing long-term toxicities. Tenofovir disoproxil fumarate (TDF) has been associated with potential nephrotoxicity. The aim of our study was to assess the impact of switching from TDF to tenofovir alafenamide (TAF) on functional nephropathy and lipid parameters in a real-life setting.

METHODS

We retrospectively analysed data from 347 HIV-infected patients switching from a TDF- to a TAF-containing regimen between April and December 2016. Sociodemographic, clinical and laboratory data were collected at TDF-to-TAF switch, and at 3 and 6 months thereafter. Proteinuria and albuminuria were classified according to Kidney Diseases Improving Global Outcomes (KDIGO) guidelines.

RESULTS

At time of switch, moderately and severely increased proteinuria was detected in 32% and 8% of patients, respectively; however, urine dipstick analysis was negative in 84% and 42%, respectively. Moderately and severely increased albuminuria was found in 17% and 3% of patients, respectively. In patients with a urinary protein-to-creatinine ratio (UPCR) ≥ 150 mg/g, the mean value declined from 416 mg/g at baseline to 272 mg/g (P < 0.001) and 242 mg/g (P < 0.001) after 3 and 6 months, respectively. Patients with an albumin-to-creatinine ratio (UACR) ≥ 30 mg/g showed no significant decrease of albuminuria. Mean total cholesterol increased from 187 mg/dL at baseline to 202 (P < 0.001) and 208 mg/dL (P < 0.001) at 3 and 6 months, respectively, and mean low-density lipoprotein (LDL) cholesterol increased from 114 mg/dL at baseline to 124 (P < 0.001) and 128 mg/dL (P < 0.001), respectively. As mean high-density lipoprotein (HDL) cholesterol increased from 50 mg/dL at baseline to 54 (P < 0.001) and 57 mg/dL (P < 0.001) at 3 and 6 months, respectively, the LDL:HDL ratio remained stable.

CONCLUSIONS

In an aging HIV-infected cohort, proteinuria and albuminuria were common findings and were underdiagnosed via urine dipstick. Our real-life data suggest that laboratory markers of moderately/severely increased proteinuria improved after TDF-to-TAF-switch. Lipid profiles were not aggravated. Long-term follow-up is needed to determine the clinical benefit of the TDF-to-TAF switch.

摘要

目的

开发新型抗逆转录病毒药物旨在降低长期毒性。富马酸替诺福韦二吡呋酯(TDF)与潜在的肾毒性有关。本研究的目的是评估在真实环境中从 TDF 转换为替诺福韦艾拉酚胺(TAF)对肾功能障碍和脂质参数的影响。

方法

我们回顾性分析了 2016 年 4 月至 12 月期间 347 例从 TDF 转换为含 TAF 方案的 HIV 感染患者的数据。在 TDF 转换为 TAF 时以及之后的 3 个月和 6 个月收集了社会人口统计学、临床和实验室数据。根据肾脏疾病改善全球结局(KDIGO)指南对蛋白尿和白蛋白尿进行分类。

结果

转换时,分别有 32%和 8%的患者出现中度和重度蛋白尿,但尿沉渣分析分别为 84%和 42%阴性。分别有 17%和 3%的患者出现中度和重度白蛋白尿。在尿蛋白与肌酐比值(UPCR)≥150mg/g 的患者中,平均值从基线时的 416mg/g 分别下降至 3 个月时的 272mg/g(P<0.001)和 6 个月时的 242mg/g(P<0.001)。UACR≥30mg/g 的患者白蛋白尿无显著下降。总胆固醇平均值从基线时的 187mg/dL 分别升高至 3 个月时的 202mg/dL(P<0.001)和 6 个月时的 208mg/dL(P<0.001),低密度脂蛋白(LDL)胆固醇平均值从基线时的 114mg/dL 分别升高至 124mg/dL(P<0.001)和 128mg/dL(P<0.001)。高密度脂蛋白(HDL)胆固醇平均值从基线时的 50mg/dL 分别升高至 3 个月时的 54mg/dL(P<0.001)和 6 个月时的 57mg/dL(P<0.001),而 LDL:HDL 比值保持稳定。

结论

在老龄化的 HIV 感染患者中,蛋白尿和白蛋白尿是常见的发现,但通过尿沉渣检测被漏诊。我们的真实数据表明,TDF 转换为 TAF 后,实验室指标中度/重度蛋白尿得到改善。血脂谱没有恶化。需要进行长期随访以确定 TDF 转换为 TAF 的临床益处。

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