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.