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Summary: Background: In two phase 3 studies, tenofovir alafenamide (TAF) showed non‐inferior efficacy versus tenofovir disoproxil fumarate (TDF), with more favourable renal and bone safety in patients with chronic hepatitis B (CHB). Aims: Here, we report the studies' final 8‐year results. Methods: CHB patients (hepatitis B e antigen [HBeAg]‐negative and HBeAg‐positive) were randomised (2:1) to double‐blind TAF 25 mg/day or TDF 300 mg/day for up to 3 years, followed by open‐label (OL) TAF through year 8. Virological, biochemical, serological and fibrosis responses, and safety, including bone and renal parameters, were evaluated. Resistance to TAF was assessed annually by deep sequencing of polymerase/reverse transcriptase and by phenotyping. Results: Among 1298 patients randomised to double‐blind TAF (n = 866) or double‐blind TDF (n = 432), 775 in the TAF group and 382 in the TDF group received OL TAF, including 180 and 202 who switched from TDF to TAF at year 2 (TDF2y → TAF6y) or year 3 (TDF3y → TAF5y), respectively. At year 8, among patients in the TAF8y, TDF2y → TAF6y and TDF3y → TAF5y groups, 69%, 66% and 73% (missing‐equals‐failure analysis) and 95%, 94% and 97% (missing‐equals‐excluded) of patients, respectively, achieved HBV DNA <29 IU/mL. Estimated glomerular filtration rate (Cockcroft‐Gault method; eGFRCG) and hip/spine bone mineral density (BMD) remained stable in patients receiving double‐blind/OL TAF, with only small declines at year 8. Decreases in eGFRCG and hip/spine BMD observed during double‐blind TDF improved after switching to OL TAF. No patients developed resistance to TAF. Conclusion: Long‐term TAF treatment exhibited favourable safety and tolerability with high rates of viral suppression and no development of resistance. ClinicalTrials.gov numbers NCT01940341 and NCT01940471. [ABSTRACT FROM AUTHOR]

Summary: Background: Patients with chronic hepatitis B (CHB) who switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) show changes in lipid profiles. Aim: To evaluate how these changes affect cardiovascular risk. Methods: This pooled analysis, based on two large prospective studies, evaluated fasting lipid profiles of patients with CHB who were treated with TAF 25 mg/day or TDF 300 mg/day for 96 weeks. Patients who fulfilled the American College of Cardiology criteria (age 40–79 years, high‐density lipoprotein [HDL] 20–100 mg/dL, total cholesterol [TC] 130–320 mg/dL and systolic blood pressure 90–200 mmHg) required to assess 10‐year atherosclerotic cardiovascular disease (ASCVD) risk with baseline lipid data and at least one post‐baseline measurement were included in the ASCVD‐risk population. The 10‐year ASCVD risk was calculated for patients in this population, and changes from baseline to Week 96 were assessed using intermediate‐ (≥7.5%) and high‐risk (≥20%) cut‐offs. Results: Among 1632 patients, 620 (38%) met the criteria for the ASCVD‐risk population. At Week 96, fasting levels of all lipids, except TC:HDL ratio, were lower with TDF than TAF. No significant increase was observed in overall ASCVD risk or in any ASCVD‐risk categories during the 96‐week treatment period compared with baseline. A similar proportion of patients in the TAF and TDF treatment groups (1.3% and 2.3%, respectively; p = 0.34) reported cardiovascular events. Conclusion: Despite on‐treatment differences in lipid profiles with TAF and TDF, predicted cardiovascular risk and clinical events were similar for both groups after 96 weeks. [ABSTRACT FROM AUTHOR]

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., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)