Abstract and Introduction
Objectives: The aim of the study was to analyse and compare estimated glomerular filtration rate (eGFR) slopes during exposure to tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) in individuals who initiated TAF, regardless of prior regimen, before October 2016.
Methods: An observational cohort study was conducted at 11 clinics in the UK and Ireland. Mixed effects models with random intercept and time terms fitted were used to generate and compare eGFR slopes while participants were exposed to TDF and TAF, with adjustment for age, eGFR at TDF/TAF initiation, gender, ethnicity, and time-updated CD4 cell count and HIV RNA measurements.
Results: Data were available for 357 subjects (median age 50 years; 80% male; 82% white/other ethnicity; 51% men who have sex with men; median nadir CD4 count 216 cells/μL). The median duration of exposure to TAF was 2.0 (interquartile range 1.6, 2.3) years. At TAF initiation, the median CD4 count was 557 cells/μL, the median eGFR was 80 mL/min/1.73 m2, and 86% had suppressed HIV infection. The mean adjusted eGFR slope during TDF and TAF exposure was −2.08 [95% confidence interval (CI) −2.24, −1.92] and 1.18 (95% CI 0.20, 1.52) mL/min/1.73 m2/year, respectively (P < 0.001). Individuals who experienced rapid eGFR decline (> 3 or 5 mL/min/1.73 m2/year) while receiving TDF experienced significant eGFR recovery while on TAF (P < 0.001).
Conclusions: Significant improvement in eGFR slope was observed in patients who switched from TDF- to TAF-containing antiretroviral regimens. These data provide further support for the renal safety of TAF, and for switching those who experience progressive worsening of renal function from TDF to TAF.
Tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) are both pro-drugs of tenofovir, a potent and widely used nucleotide reverse transcriptase inhibitor for treating HIV and hepatitis B virus infections. TDF has been associated with adverse effects on the kidney, including chronic kidney disease (CKD), proteinuria, rapid decline in estimated glomerular filtration rate (eGFR; > 3 or 5 mL/min/1.73 m2/year) and renal tubular dysfunction.[1–4] Rarely, in severe cases, tubular injury may result in proximal tubulopathy with glycosuria and phosphate wasting,[5,6] with incomplete reversibility of eGFR upon TDF discontinuation in about one-third of cases.[7,8] High plasma tenofovir concentrations have been linked to eGFR decline,[9,10] and eGFR decline commonly precedes the onset of tubulopathy.
Use of TAF results in approximately 10-fold lower plasma tenofovir exposure compared with TDF, resulting in an improved renal safety profile, with no cases of proximal tubulopathy reported in clinical trials that enrolled more than 6000 individuals, and less impact on renal tubular biomarkers. In a study of 242 individuals with HIV infection and impaired kidney function, TAF-containing regimens were associated with stable renal function (no change in median eGFR) over 96 weeks and, in those who switched off TDF, statistically significant improvements in proteinuria. Of note, this study required participants to have stable renal function (defined as a creatinine measurement at screening which was < 25% above a measurement recorded in the past 3 months). Thus, it remains unclear whether a switch from TDF to TAF abrogates eGFR decline in those who experience rapid eGFR decline while receiving TDF-containing antiretroviral therapy (ART).
We compared eGFR slopes on TDF and TAF in people with HIV infection who received TAF prior to or shortly after it became commercially available in the UK and Ireland, irrespective of the ART regimen at TAF initiation. We hypothesized that a substantial proportion of these individuals would have experienced eGFR decline while receiving TDF, and that eGFR slopes would have improved in people who switched from TDF- to TAF-containing ART.
HIV Medicine. 2020;21(9):607-612. © 2020 Blackwell Publishing