Tenofovir Alafenamide for Drug-Resistant Hepatitis B: A Randomized Trial for Switching from Tenofovir Disoproxil Fumarate.

Abstract

BACKGROUND & AIMS\nIt remains unknown whether tenofovir alafenamide (TAF) could replace tenofovir disoproxil fumarate (TDF) in patients with drug-resistant hepatitis B virus (HBV).\n\n\nMETHODS\nIn this multi-center randomized non-inferiority trial, 174 patients with HBV resistant to multiple drugs (lamivudine, entecavir, and/or adefovir) under TDF monotherapy for ≥96 weeks were randomized 1:1 to switch to TAF (n=87) or continue TDF (n=87) for 48 weeks. The primary endpoint was proportion of patients with HBV DNA<60 IU/mL at week 48.\n\n\nRESULTS\nAt baseline, 84 and 80 patients had HBV DNA <60 IU/mL in the TAF and TDF groups, respectively. At week 48, the proportion of patients with HBV DNA<60 IU/mL was 98.9% (86/87) in TAF group, showing non-inferiority to TDF group (97.7%, 85/87; difference, 1.1%; 95% confidence interval, -2.7% to 5.0%). Changes in median ALT at week 48 from baseline were statistically different between TAF and TDF groups (-3 IU/L vs. +2 IU/L; P=.02). TAF group showed a statistically greater increase in bone mineral density at spine (+1.84% vs. +0.08%; P=.01) and numerically higher increase in mean estimated glomerular filtration rate (+8.2% vs. +4.5%; P=.06), compared with TDF group. TAF group, compared with TDF group, showed significantly greater increases in mean body weight (0.71 vs. -0.37 kg; P=.01) and total, LDL, and HDL cholesterol levels (P<.001 for all) at week 48 from baseline.\n\n\nCONCLUSIONS\nTAF could be substituted for TDF in patients with multidrug-resistant HBV for improved bone and renal safety without a loss of efficacy. However, increases in body weight and cholesterol levels with TAF treatment would be a concern.