Background: Tenofovir (TFV) is renally eliminated, and the prodrug, tenofovir disoproxil fumarate (TDF), has been associated with renal toxicity and reduced bone mineral density (BMD), and must be dose adjusted in patients with estimated glomerular filtration rate (eGFR) < 50mL/min. Tenofovir alafenamide (TAF) is a novel prodrug of TFV that is not renally eliminated and at clinical doses results in 90% lower plasma TFV levels as compared to TDF. The safety and efficacy of a once-daily single tablet regimen of elvitegravir, cobicistat, emtricitabine, and TAF (E/C/F/TAF) was assessed in HIV-1 infected patients with mild to moderate renal impairment.
Methods: Virologically suppressed adults with stable eGFRCG (Cockroft”‘Gault) of 30 to 69 mL/min had their treatment switched from both TDF- and non-TDF-containing regimens to open-label E/C/F/TAF. Week 24 efficacy and safety data are described, including tests of renal function and BMD. Actual GFR (aGFR) was assessed with iohexol clearance in a subset of subjects.
Results: Of 242 subjects enrolled and dosed, mean age was 58 years (range: 24 – 82), 18% Black, 39% hypertension, and 14% diabetes. 65% were taking TDF-containing regimens prior to switch. At baseline, median eGFRC-G was 55.6 mL/min (33% eGFRC-G 30-49 mL/min). 95% of subjects maintained HIV-1 VL <50 c/mL at Week 24 (FDA Snapshot). At Week 24, the median (Q1, Q3) change from baseline eGFRC-G was -0.4 (-4.7, 4.5) mL/min, eGFR-cystatin C 3.8 (-4.8, 11.2) mL/min/1.73m2, and aGFR (n=32, 68.8% TDF at baseline) was 0.1 (-4.3, 4.4) mL/min, indicating that GFR was not affected by E/C/F/TAF. Two subjects (0.8%) discontinued study drug for decreased GFR by eGFRC-G and eGFR-cystatin C, neither with evidence of renal tubulopathy. The prevalence of clinically significant proteinuria (UPCR > 200 mg/g) and albuminuria (UACR ≥ 30 mg/g) decreased from 42% to 21% and 49% to 27%, respectively. Significant decreases in urine retinol binding protein to creatinine ratio, beta”‘2”‘microglobulin to creatinine ratio, and fractional excretion of uric acid were observed (p<0.001 for all). Hip and spine BMD percentage change from baseline to Week 24 was 0.74% (-0.71, 2.03) and 1.27% (-0.44, 3.83) (median, IQR), respectively.
Conclusions: These 24 week data support the virologic efficacy and renal and bone safety of once daily single-tablet E/C/F/TAF for use in HIV+ patients with mild and moderate renal impairment (eGFR 30 to 69 mL/min). Switch to E/C/F/TAF was associated with no change in aGFR and with reductions in proteinuria.