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Longer-Term Renal Safety of Tenofovir Alafenamide vs Tenofovir Disoproxil Fumarate
Bart J. Rijnders1; Frank A. Post2; Armin Rieger3; Eugenio Teofilo4; David Wohl5; Paul E. Sax6; Susan Guo7; Andrew Cheng7; Moupali Das7; Marshall Fordyce7
1Erasmus Univ Med Cntr, Rotterdam, Netherlands;2King's Coll Hosp NHS Fndn Trust, London, UK;3Med Univ of Vienna, Vienna, Austria;4Hosp dos Capuchos, Centro Hospar de Lisboa Central, Lisbon, Portugal;5Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA;6Brigham and Women's Hosp, Harvard Med Sch, Boston, MA, USA;7Gilead Sciences, Foster City, CA, USA
Compared with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) results in a 91% reduction in plasma tenofovir (TFV) exposure and has demonstrated less impact on surrogate markers of renal and bone health in multiple populations, but the clinical impact of these differences has not been fully characterized.
Treatment naïve HIV-1+ adults were randomized 1:1 to a single tablet regimen coformulating elvitegravir, cobicistat, emtricitabine, with TAF (E/C/F/TAF) or TDF (E/C/F/TDF) once daily in two double blind studies. Assessments of renal function included serum creatinine and estimated GFR by Cockcroft-Gault (eGFRCG), and 4 measures of proteinuria: urine protein:creatinine (UPCR), urine albumin:creatinine (UACR), retinol binding protein:creatinine (RBP:Cr), and beta-2-microglobulin:creatinine (β-2-Mg:Cr). A post-hoc analysis of renal events in both studies through 96 weeks is described.
Combined, the two studies randomized and treated 1,733 participants. Through 96 weeks, change from baseline eGFRCG, UPCR, UACR, RBP:Cr, and β-2-Mg:Cr, all favored E/C/F/TAF (p<0.001). There were no discontinuations for renal adverse events (AE) or cases of proximal tubulopathy in the E/C/F/TAF arm, while 6 participants discontinued due to a renal AE and 1 participant had subclinical tubulopathy in the E/C/F/TDF arm.
Fewer participants in the E/C/F/TAF arm had clinical events of new onset chronic kidney disease (CKD) and acute kidney injury (AKI, 50% decrease in eGFRCG), though differences were not statistically significant, while the differences in participants with significant proteinuria (UPCR >200 mg/g) and albuminuria (UACR >30 mg/g) were statistically significant (Table).
Through 96 weeks, biomarker analysis indicated that renal tubular function was less affected by E/C/F/TAF and that clinically significant renal events were less frequent in subjects receiving E/C/F/TAF compared with those treated with E/C/F/TDF. These data provide further support for the improved renal safety profile of TAF.