Estimated Glomerular Filtration Rate Slopes on Tenofovir Alafenamide

F Ibrahim; L Campbell; AC Bailey; S Stockwell; L Waters; C Orkin; M Johnson; M Gompels; A De Burgh-Thomas; R Jones; G Schembri; PW Mallon; FA Post


HIV Medicine. 2020;21(9):607-612. 

In This Article


A total of 385 individuals initiated a TAF-containing ART regimen at one of the eight participating sites in the UK or Ireland, prior to October 2016. Twenty-eight individuals were excluded (19 accessed TAF through participation in randomized clinical trials, and no renal function data were provided for seven subjects). Thus, 357 predominantly male individuals with a median age of 50 [interquartile range (IQR) 42, 59] years were included in the analyses. At TAF initiation, the median CD4 cell count was 557 cells/μL, 86% had an undetectable HIV viral load, 8% and 8% were coinfected with hepatitis B and C viruses, respectively, 14% and 10% had hypertension and diabetes mellitus, respectively, and the median eGFR was 79.5 (IQR 62.9, 98.3) mL/min/1.73 m2. A total of 309 (87%) had prior TDF exposure; the median (IQR) age at TDF initiation was 43 (37, 51) years, and the median (IQR) CD4 count was 386 (233, 583) cells/μL. The median duration of TDF exposure was 4.8 (IQR 1.9, 7.9) years [co-administered with protease inhibitors in 107 (35%) and didanosine in four (1%) individuals], and median time between TDF discontinuation and TAF initiation was 0 (IQR 0, 5.5) months. The median follow-up on TAF was 2.0 (IQR 1.6, 2.3) years (Table 1). Ten participants discontinued TAF, for various reasons, including three renal discontinuations (0.8%); all three had stage 3b CKD which progressed to the dosing threshold of eGFR < 30 mL/min/1.73 m2 while receiving TAF.

The mean eGFR slope estimates are shown in Table 2. The 309 participants with prior TDF exposure experienced eGFR decline [mean −2.20 (95% CI −2.36 to −2.03) mL/min/1.73 m2/year] while receiving TDF and improvement in eGFR [mean +1.16 (95% CI +0.55 to +1.82) mL/min/1.73 m2/year] while receiving TAF. Adjustment for potential confounders had minimal effect on these slopes. Participants who initiated TAF some time after discontinuing TDF had experienced greater eGFR decline while receiving TDF compared to those who switched directly from TDF to TAF; both groups had significantly improved eGFR slopes on TAF vs. TDF. Those without prior TDF exposure maintained stable renal function while receiving TAF.

We then analysed eGFR slopes in participants who experienced rapid eGFR decline while receiving TDF. A total of 126 (40.8%) and 70 (22.7%) individuals experienced eGFR decline of > 3 and 5 mL/min/1.73 m2/year, respectively. Their eGFR slopes significantly improved after switch to TAF-containing ART regimens, suggesting some recovery of kidney function. Those who had experienced eGFR < 60 mL/min/1.73 m2 while receiving TDF also experienced improvements in eGFR slopes following the initiation of TAF (Table 2). Similar results were obtained in a sensitivity analysis in which eGFR measurements during the first 4 weeks of TDF/TAF exposure were excluded to account for the effects of co-administered ART on tubular secretion of creatinine (Table S1).