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Longitudinal Progression of Estimated GFR in HIV-1-Infected Patients with Normal Renal Function on Tenofovir-Based Therapy in China

Authors
  • Liu, Fang1
  • Xu, Aifang1
  • Zhao, Huaqing2
  • Yang, Zongxing3
  • Chen, Chen4
  • Ranieri, Brona4
  • Bao, Jianfeng5
  • Zheng, Guoxiang3
  • Wang, Miaochan1
  • Wang, Ying1
  • Xun, Yunhao5
  • 1 Medical Laboratory, Xixi Hospital of Hangzhou, Hangzhou
  • 2 Temple University School of Medicine, Department of Clinical Sciences, Philadelphia, PA
  • 3 Department of Infectious Diseases, Xixi Hospital of Hangzhou, Hangzhou
  • 4 Department of Neuroscience, Temple University, Philadelphia, PA
  • 5 Department of Integrated Chinese and Western Medicine, Xixi Hospital of Hangzhou, Hangzhou
Type
Published Article
Journal
Therapeutics and Clinical Risk Management
Publisher
Dove Medical Press Ltd.
Publication Date
Apr 17, 2020
Volume
16
Pages
299–310
Identifiers
DOI: 10.2147/TCRM.S243913
PMID: 32368069
PMCID: PMC7173951
Source
PubMed Central
Keywords
License
Green

Abstract

Purpose Estimated glomerular filtration rate (eGFR) decline in HIV-1-infected patients exposure to tenofovir disoproxil fumarate (TDF) has been widely assessed using linear models, but nonlinear assumption is not well validated. We constructed a retrospective cohort study to assess whether eGFR decline follows nonlinearity during antiviral therapy. Patients and Methods We examined 823 (299 of TDF users and 524 of non-TDF users) treatment-naïve HIV-1-infected participants (age ≥ 17 years, initial eGFR ≥ 90 mL/min/1.73m2). Estimated GFR trajectories were compared by one-linear and piecewise-linear mixed effects models, before and after propensity score matching, respectively. Whether the incidence of renal dysfunction (reduced renal function [RRF], eGFR < 90 mL/min/1.73 m2 and rapid kidney function decline [RKFD], eGFR > −3 mL/min/1.73 m2/year) follows nonlinearity was assessed by logistic regression. Results The median follow-up time of this study was 10 (interquartile range, 2–20) months, during which 178 (21.6%) experienced RRF, and 451 (54.8%) experienced RKFD. The slopes (mL/min/1.73 m2/year) of eGFR were −5.31 (95% CI: −6.57, −4.06) before 1.40 years, 4.83 (95% CI: 1.38, 8.28) from years 1.40 to 2.30 and −3.71 (95% CI: −5.97, −1.45) after 2.30 years among TDF users. Within years 1.40–2.30, each year of TDF exposure was associated with a 78% decreased risk of RKFD (95% CI: −91%, −49%). In comparison, eGFR increased slightly at the initiation of antiviral therapy, declined after 2.15 years (−4.96; 95% CI: −5.76, −4.17) among non-TDF users. Such a progression nonlinear trajectory was missed on the assumption of one-linearity, whether in TDF or non-TDF users. Conclusion Over the piecewise mixed-effects analyses with the advantage of revealing the true nature of the exposure outcome relationships, an interesting reverse S-shaped relationship was observed. A routine screen based on nonlinearity could be more helpful for patient management.

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