icon-    folder.gif   Conference Reports for NATAP  
 
  IAS 2015: 8th IAS Conference on
HIV Pathogenesis Treatment and Prevention
Vancouver, Canada
18-22 July 2015
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Kidney and Bone Marker Rally After TDF-to-TAF Switch for 48 Weeks
 
 
  IAS 2015, July 19-22, 2015, Vancouver
 
Mark Mascolini
 
Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) for 48 weeks improved bone mineral density (BMD) and urinary markers of kidney function in an open-label phase 3 trial involving people with impaired kidney function [1]. Actual glomerular filtration rate (GFR) did not change after the switch.
 
Renal and bone toxicities linked to TDF are well-appreciated phenomena of clinical practice. Because TAF puts less active tenofovir in plasma and more in target T cells, it has engendered better kidney and bone safety profiles when compared with TDF in randomized trials [2]. This new study is the first to assess the impact of switching from TDF or a non-TDF regimen to TAF coformulated with elvitegravir, cobicistat, and emtricitabine (E/C/F/TAF) in virally suppressed people.
 
A multicenter team recruited adults with well-controlled HIV replication taking a TDF regimen or a non-TDF regimen who changed to E/C/F/TAF. Everyone had a stable estimated glomerular filtration rate (eGFR) of 30 to 69 mL/min indicating renal impairment. The primary endpoint was change from baseline eGFR through week 24. The investigators also tracked actual GFR by iohexol clearance in a subset of participants. And they measured kidney and bone markers through 48 weeks.
 
The study involved 158 people switching from a TDF combination and 84 switching from a non-TDF regimen to E/C/F/TAF. One quarter of participants were 65 or older, 21% were women, and 18% were black. Median CD4 count stood at 632 and median eGFR at 56 mL/min. Among participants not taking TDF, 22% were taking abacavir, 7% another nucleoside, and 5% no nucleosides. More people were taking a protease inhibitor (44%) or a nonnucleoside (42%) than an integrase inhibitor (24%) or maraviroc (3%).
 
Actual GFR by iohexol clearance hardly wavered through 24 weeks in people switching from TDF or in people switching from other regimens. Through 48 weeks eGFR fell significantly in the combined arms (-1.8 mL/min) and in the non-TDF arm (-2.7 mL/min) when calculated by the CKD-EPI Cr method, but not by the Cockroft-Gault method. eGFR rose significantly through 48 weeks in the combined arm (+1.6 mL/min) and the TDF arm (+2.7 mL/min) when calculated by the CKD-EPI cystatin C method.
 
Proteinuria dropped significantly through 48 weeks in people switching from TDF but not from non-TDF regimens. The proportion of participants with proteinuria above 200 mg/g dropped significantly from 41% to 16% through 48 weeks in the combined arms and from 47% to 13% in the TDF arm. The drop from 29% to 22% in the non-TDF group was not significant. The proportion of participants with albuminuria above 30 mg/g fell from 49% to 26% in the combined arms (significant), from 55% to 22% in the TDF arm (significant), and from 37% to 34% in the non-TDF arm (not significant).
 
Through week 48 spine BMD rose 2.29% in the combined arms (P < 0.05), 2.95% in the TDF arm (P < 0.05), and 0.99% in the non-TDF arm (not significant). Respective hip BMD changes were 1.47% (P < 0.05), 1.85% (P < 0.05), and 0.70% (not significant).
 
Total to high-density lipoprotein cholesterol ratio rose (worsened) 0.3 through 48 weeks in the TDF group (P < 0.001) and 0.2 (P = 0.010) in the non-TDF group. Those change in the TDF arm, the researchers observed, is consistent with findings that circulating tenofovir cuts cholesterol levels.
 
In investigators proposed that their findings "support the renal and bone safety of once daily single-tablet E/C/F/TAF for adults with HIV and renal impairment (eGFR 30 to 69 mL/min)."
 
References
 
1. Gupta S, Pozniak A, Arribas J, et al. Subjects with renal impairment switching from tenofovir disoproxil fumarate to tenofovir alafenamide have improved renal and bone safety through 48 weeks. IAS 2015. 8th Conference on HIV Pathogenesis, Treatment and Prevention. July 19-22, 2015. Vancouver. Abstract TUAB0103.
 
2. Sax PE, Wohl D, Yin MT, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. Lancet. 2015;385:2606-2615.