Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Patients With Renal Impairment: 48-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study

Anton Pozniak, Jose R Arribas, Joseph Gathe, Samir K Gupta, Frank A Post, Mark Bloch, Anchalee Avihingsanon, Gordon Crofoot, Paul Benson, Kenneth Lichtenstein, Moti Ramgopal, Ploenchan Chetchotisakd, Joseph M Custodio, Michael E Abram, Xuelian Wei, Andrew Cheng, Scott McCallister, Devi SenGupta, Marshall W Fordyce, GS-US-292-0112 Study Team, Anton Pozniak, Jose R Arribas, Joseph Gathe, Samir K Gupta, Frank A Post, Mark Bloch, Anchalee Avihingsanon, Gordon Crofoot, Paul Benson, Kenneth Lichtenstein, Moti Ramgopal, Ploenchan Chetchotisakd, Joseph M Custodio, Michael E Abram, Xuelian Wei, Andrew Cheng, Scott McCallister, Devi SenGupta, Marshall W Fordyce, GS-US-292-0112 Study Team

Abstract

Background: Tenofovir alafenamide (TAF) is a novel tenofovir prodrug with improved renal and bone safety compared with TDF-containing regimens. We report the 48 week safety and efficacy of a once-daily single tablet regimen of elvitegravir 150 mg (E), cobicistat 150 mg (C), emtricitabine 200 mg (F), and TAF 10 mg (E/C/F/TAF) in HIV-1-infected patients with mild to moderate renal impairment.

Methods: We enrolled virologically suppressed HIV-1-infected subjects with estimated creatinine clearance (CrCl) 30-69 mL/min in a single-arm, open-label study to switch regimens to E/C/F/TAF. The primary endpoint was the change from baseline in glomerular filtration rate estimated using various formulae. This study is registered with ClinicalTrials.gov, number NCT01818596.

Findings: We enrolled and treated 242 patients with mean age 58 years, 18% Black, 39% hypertension, 14% diabetes. Through week 48, no significant change in estimated CrCl was observed. Two patients (0.8%) discontinued study drug for decreased creatinine clearance, neither had evidence of renal tubulopathy and both had uncontrolled hypertension. Subjects had significant improvements in proteinuria, albuminuria, and tubular proteinuria (P < 0.001 for all). Hip and spine bone mineral density significantly increased from baseline to week 48 (mean percent change +1.47 and +2.29, respectively, P < 0.05). Ninety-two percent (222 patients) maintained HIV-1 RNA <50 copies per milliliter at week 48.

Interpretation: Switch to E/C/F/TAF was associated with minimal change in GFR. Proteinuria, albuminuria and bone mineral density significantly improved. These data support the efficacy and safety of once daily E/C/F/TAF in HIV+ patients with mild or moderate renal impairment without dose adjustment.

Conflict of interest statement

A.P. reports receiving grants and speaker fees from Gilead, ViiV, BMS, Janssen, and Merck. J.R.A. reports receiving grants and speaker fees from Gilead, Viiv, BMS, Janssen, and Abbvie. S.K.G. reports receiving grants and speaker fees from Gilead, BMS, Janssen, and Merck. F.A.P. reports receiving grants and speaker fees from Gilead, Janssen, ViiV, Abbvie, and MSD. M.B. reports receiving grants and speaker fees from Gilead, ViiV, Abbvie, MSD, Lilly, Novartis, and Amgen. G.C. reports receiving grants and speaker fees from Gilead, Janssen, ViiV, and Merck. J.G., P.B., K.L., and M.R. report receiving grants from Gilead. P.C. reports receiving grants and speaker fees from Gilead and MSD. A.A. reports no conflicts to disclose. J.M.C., M.E.A., X.W., A.C., S.M., D.S., and M.W.F. are employees of Gilead Sciences.

Figures

FIGURE 1
FIGURE 1
A, Proteinuria: change from baseline to week 48. B, Significant proteinuria: baseline to week 48. C, Significant albuminuria: baseline to week 48.
FIGURE 2
FIGURE 2
A, BMD: mean change from baseline to week 48. B, Proportions of patients with BMD changes.

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Source: PubMed

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