Journal Article

Long-Term Treatment With Tenofovir Alafenamide for Chronic Hepatitis B Results in High Rates of Viral Suppression and Favorable Renal and Bone Safety

Agarwal, Kosh, Izumi, Namiki, Seto, Wai-Kay, Osinusi, Anu, Lim, Young-Suk, Flaherty, John F., Fung, Scott, Ma, Xiaoli, Buti, Maria, Pan, Calvin Q., Shalimar, Janssen, Harry L.A., Abdurakhmanov, Dzhamal, Camus, Gregory, Chuang, Wan-Long, Wang, Hongyuan, Gane, Edward, Chan, Henry L.Y., Celen, Mustafa K., Marcellin, Patrick, Caruntu, Florin, Abramov, Frida, Brunetto, Maurizia, Jabłkowski, Maciej

2024

Overview

INTRODUCTION:The results from 2 phase 3 studies, through 2 years, in chronic hepatitis B infection showed tenofovir alafenamide (TAF) had similar efficacy to tenofovir disoproxil fumarate (TDF) with superior renal and bone safety. We report updated results through 5 years.METHODS:Patients with HBeAg-negative or HBeAg-positive chronic hepatitis B infection with or without compensated cirrhosis were randomized (2:1) to TAF 25 mg or TDF 300 mg once daily in double-blind (DB) fashion for up to 3 years, followed by open-label (OL) TAF up to 8 years. Efficacy (antiviral, biochemical, and serologic), resistance (deep sequencing of polymerase/reverse transcriptase and phenotyping), and safety, including renal and bone parameters, were evaluated by pooled analyses.RESULTS:Of 1,298 randomized and treated patients, 866 receiving TAF (DB and OL) and 432 receiving TDF with rollover to OL TAF at year 2 (n = 180; TDF→TAF3y) or year 3 (n = 202; TDF→TAF2y) were included. Fifty (4%) TDF patients who discontinued during DB were excluded. At year 5, 85%, 83%, and 90% achieved HBV DNA <29 IU/mL (missing = failure) in the TAF, TDF→TAF3y, and TDF→TAF2y groups, respectively; no patient developed TAF or TDF resistance. Median estimated glomerular filtration rate (by using Cockcroft-Gault) declined <2.5 mL/min, and mean declines of <1% in hip and spine bone mineral density were seen at year 5 in the TAF group; patients in the TDF→TAF groups had improvements in these parameters at year 5 after switching to OL TAF.DISCUSSION:Long-term TAF treatment resulted in high rates of viral suppression, no resistance, and favorable renal and bone safety.

• Publisher: Wolters Kluwer,Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
• Subject: Adenine - administration & dosage / Adenine - adverse effects / Adenine - analogs & derivatives / Adenine - therapeutic use / Adult / Alanine - therapeutic use / Antigens / Antiretroviral drugs / Antiviral Agents - therapeutic use / Antiviral drugs / Bone Density - drug effects / Double-Blind Method / Drug dosages / Drug Resistance, Viral / Female / Glomerular Filtration Rate - drug effects / Hepatitis B / Hepatitis B e Antigens - blood / Hepatitis B virus - genetics / Hepatitis B, Chronic - drug therapy / Humans / Kidney - drug effects / Liver / Liver cancer / Liver cirrhosis / Liver diseases / Male / Middle Aged / Population / Tenofovir - analogs & derivatives / Tenofovir - therapeutic use / Treatment Outcome / Viral Load - drug effects