Nonlinear Trajectory of Estimated GFR Progression in HIV-Positive Patients with Normal Renal Function on Tenofovir - based Therapy in Asia: a retrospective observational cohort study

Background: Estimated glomerular filtration rate (eGFR) trajectory in HIV-1-infected patients on tenofovir disoproxil fumarate (TDF) therapy has been widely estimated using linear models, but this linearity assumption is not well validated and the nonlinearity of eGFR change remains unknown in Asians with initially normal renal function. Methods Estimated GFR trajectories were compared by one-linear and piecewise-linear mixed effects models, before and after propensity matching, respectively. Whether the incidence of renal dysfunction (reduced renal function [RRF], eGFR -3 mL/min/1.73 m²/year) follows nonlinearity was assessed by logistic regression. Results In this Chinese observational cohort, we examined 823 (299 of TDF users and 524 of non-TDF users) treatment-naïve HIV-1-infected participants (age≥17 years) with first eGFR greater than 90 mL/min/1.73m². The median follow-up time was 10 (interquartile range [IQR], 2-20) months, during which 178 (21.6%) experienced RRF, and 451 (54.8%) experienced RKFD. In nonlinear adjusted model, the eGFR of TDF users decreased over time before 1.40 years (-5.31 mL/min/1.73 m²/year; 95% CI: -6.57, -4.06), and after 2.30 years (-3.71 mL/min/1.73 m²/year; 95% CI: -5.97, -1.45). However, the eGFR significantly increased from years 1.40 to 2.30 (4.83 mL/min/1.73 m²/year; 95% CI:1.38, 8.28). Within this particular time frame, 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 mL/min/1.73 m²/year; 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 For HIV-1-infected Asians initiated antiviral therapy with normal renal function, the nonlinearity of renal function do exist. Routine screen based on nonlinear progression of eGFR could be helpful for clinical management and patient care.