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

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.

Keywords:

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

Abbreviations

TDF, Tenofovir disoproxil fumarate; eGFR, Estimated glomerular filtration rate; RRF, Reduced renal function; RKFD, Rapid kidney function decline; IQR, Interquartile range; HIV, Human immunodeficiency virus-1; ART, Antiretroviral therapy; CKD, Chronic kidney disease; SCr, Serum creatinine; MDRD, Modification of diet in renal disease; ARVs, Antiretrovirals; 3TC, Lamivudine; FTC, Emtricitabine; NVP, Nevirapine; EFV, Efavirenz; AZT, Zidovudine; d4T, Stavudine; BMI, Body mass index; PSM, Propensity score matching; GAM, Generalized additive model; GEE, Generalized estimating equation; OR, Odds ratio; WHO, World health organization; NA, Not applicable; CI, Confidence interval; MDR-TB, Multi-drug-resistant tuberculosis.

Data Sharing Statement

The data set used for this manuscript will be available from the corresponding author upon reasonable request.

Ethics and Consent Statement

This study was approved by the Institutional Review Board of Xixi Hospital. All data were anonymized to comply with the provisions of personal data protection legislation. Due to the retrospective nature of this study and due to the fact that only historical medical data were collected, written informed consent was not required.

Acknowledgments

We thank all study participants and staff of all participating sites.

Author Contributions

All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no competing interests in this work.

Additional information

Funding

The study did not need and was not funded.