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

Abstract

Fang Liu,1 Aifang Xu,1 Huaqing Zhao,2 Zongxing Yang,3 Chen Chen,4 Brona Ranieri,4 Jianfeng Bao,5 Guoxiang Zheng,3 Miaochan Wang,1 Ying Wang,1 Yunhao Xun5 1Medical Laboratory, Xixi Hospital of Hangzhou, Hangzhou, People’s Republic of China; 2Temple University School of Medicine, Department of Clinical Sciences, Philadelphia, PA, USA; 3Department of Infectious Diseases, Xixi Hospital of Hangzhou, Hangzhou, People’s Republic of China; 4Department of Neuroscience, Temple University, Philadelphia, PA, USA; 5Department of Integrated Chinese and Western Medicine, Xixi Hospital of Hangzhou, Hangzhou, People’s Republic of ChinaCorrespondence: Yunhao XunDepartment of Integrated Chinese and Western Medicine, Xixi Hospital of Hangzhou, Zhejiang Chinese Medical University Affiliated Sixth Hospital, 2 Hengbu Road, Hangzhou 310023, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: 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.Keywords: nonlinear trajectory, renal function, human immunodeficiency virus-1

Keywords

• nonlinear trajectory
• renal function
• human immunodeficiency virus-1