Emtricitabine

Hepatitis B virus

Lamivudine

HBsAg

Virology

Antiretroviral therapy

Viral load

Tenofovir alafenamide

Hepatitis B

Human immunodeficiency virus (HIV)

Internal medicine

Entecavir

Confidence interval

Medicine

Gastroenterology

Virus

HBeAg

Randomized controlled trial

Clinical Gastroenterology and Hepatology

It remains unknown whether tenofovir alafenamide (TAF) could replace tenofovir disoproxil fumarate (TDF) in patients with drug-resistant hepatitis B virus (HBV).In this multicenter 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.At 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 alanine aminotransferase 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. Compared with TDF group, TAF group showed significantly greater increases in mean body weight (0.71 vs -0.37 kg; P = .01) and total, low-density lipoprotein, and high-density lipoprotein cholesterol levels (P < .001 for all) at week 48 from baseline.TAF 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. ClinicalTrials.gov no.: NCT03241641.

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