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

• Published in: The American journal of gastroenterology Vol. 119; no. 3; pp. 486 - 496
• Main Authors: Chan, Henry L.Y., Buti, Maria, Lim, Young-Suk, Agarwal, Kosh, Marcellin, Patrick, Brunetto, Maurizia, Chuang, Wan-Long, Janssen, Harry L.A., Fung, Scott, Izumi, Namiki, Abdurakhmanov, Dzhamal, Jabłkowski, Maciej, Celen, Mustafa K., Ma, Xiaoli, Caruntu, Florin, Flaherty, John F., Abramov, Frida, Wang, Hongyuan, Camus, Gregory, Osinusi, Anu, Pan, Calvin Q., Shalimar, Seto, Wai-Kay, Gane, Edward
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Wolters Kluwer 01.03.2024; Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
• Subjects: 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; Chronic hepatitis B virus infection; viremia reduction; bone mineral density; tenofovir alafenamide; tenofovir disoproxil fumarate
• ISSN: 0002-9270; 1572-0241; 1572-0241
• DOI: 10.14309/ajg.0000000000002468

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.