{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:21:50Z","timestamp":1787566910910,"version":"build-2736575974"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82570707"],"award-info":[{"award-number":["82570707"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370604"],"award-info":[{"award-number":["82370604"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018534","name":"Medical Innovation Project of Fujian Province","doi-asserted-by":"publisher","award":["2023Y9269"],"award-info":[{"award-number":["2023Y9269"]}],"id":[{"id":"10.13039\/501100018534","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2023J01239"],"award-info":[{"award-number":["2023J01239"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014125","name":"Fujian Provincial Health Commission","doi-asserted-by":"publisher","award":["2025CXA058"],"award-info":[{"award-number":["2025CXA058"]}],"id":[{"id":"10.13039\/501100014125","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010651","name":"Fujian Normal University","doi-asserted-by":"publisher","award":["2025YJRHPD001"],"award-info":[{"award-number":["2025YJRHPD001"]}],"id":[{"id":"10.13039\/501100010651","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pradefovir mesylate (PDV; approved in China in 2024) and tenofovir amibufenamide (TMF; approved in China in 2021) are novel hepatocyte-targeted nucleotide prodrugs recently approved in China. Their clinical positioning relative to the guideline-endorsed benchmark tenofovir alafenamide (TAF) for chronic hepatitis B management remains undefined, particularly regarding renal\/bone safety and drug-drug interaction profiles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To synthesize available evidence and propose a pragmatic treatment selection framework.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Narrative review with systematic literature search of Phase 2\/3 randomized trials and observational real-world cohort studies (\u226548 weeks follow-up, n \u2265 100) comparing PDV or TMF with TDF or TAF, with explicit evidence quality classification. Methods: Systematic review with qualitative synthesis of Phase 2\/3 trials and observational cohorts comparing PDV or TMF with TDF or TAF. Risk of bias (RoB 2, NOS) and GRADE certainty were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TMF demonstrated noninferior antiviral efficacy versus TDF through Week 96 with superior renal and bone safety. TMF demonstrated noninferior antiviral efficacy versus TDF through Week 96, with improved renal and bone safety profiles compared with TDF. Retrospective real-world comparisons suggest comparable efficacy to TAF; however, prospective confirmation is needed. PDV demonstrated comparable HBV DNA suppression to TDF at Week 24, with sustained efficacy and favorable safety through Week 96 in Phase 3 trials PDV showed comparable HBV DNA suppression to TDF at Week 24, with Phase 3 data at Weeks 48 and 96 now available in Chinese CHB patients. PDV\u2019s CYP3A4-dependent activation creates clinically significant drug-drug interaction potential, whereas TMF and TAF utilize non-CYP pathways with favorable interaction profiles. PDV\u2019s CYP3A4-dependent activation raises the theoretical possibility of drug-drug interactions based on\n                      <jats:italic>in vitro<\/jats:italic>\n                      metabolic data, whereas TMF and TAF utilize non-CYP pathways with favorable interaction profiles.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Based on currently available evidence, TMF represents a potentially viable TAF alternative for patients with renal\/bone risk or anticipated long-term therapy, though definitive therapeutic equivalence requires prospective head-to-head randomized trials. PDV remains an emerging option requiring cautious implementation pending further characterization of its long-term durability, resistance barrier, and drug-drug interaction profile. Conclusion: TMF may represent an alternative to TAF for patients with renal\/bone risk or anticipated long-term therapy, though definitive equivalence requires prospective head-to-head randomized trials. PDV offers comparable short-term efficacy to TDF, with longer-term data now available; continued follow-up will define its role among nucleotide prodrugs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1862886","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T08:35:27Z","timestamp":1787560527000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pradefovir mesylate and tenofovir amibufenamide for chronic hepatitis B: a systematic review and pragmatic treatment algorithm"],"prefix":"10.3389","volume":"17","author":[{"given":"Shuqi","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Infectious Disease, Clinical Medical Research Center for Bacterial and Fungal Infectious Diseases of Fujian Province, Fujian Medical University Affiliated First Quanzhou Hospital","place":["Quanzhou, Fujian, China"]},{"name":"Key Laboratory of Screening and Control of Infectious Diseases (Quanzhou Medical College), Fujian Provincial University","place":["Quanzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liting","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Clinical Medical Research Center for Bacterial and Fungal Infectious Diseases of Fujian Province, Fujian Medical University Affiliated First Quanzhou Hospital","place":["Quanzhou, Fujian, China"]},{"name":"Key Laboratory of Screening and Control of Infectious Diseases (Quanzhou Medical College), Fujian Provincial University","place":["Quanzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zimei","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Clinical Medical Research Center for Bacterial and Fungal Infectious Diseases of Fujian Province, Fujian Medical University Affiliated First Quanzhou Hospital","place":["Quanzhou, Fujian, China"]},{"name":"Key Laboratory of Screening and Control of Infectious Diseases (Quanzhou Medical College), Fujian Provincial University","place":["Quanzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueping","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Clinical Medical Research Center for Bacterial and Fungal Infectious Diseases of Fujian Province, Fujian Medical University Affiliated First Quanzhou Hospital","place":["Quanzhou, Fujian, China"]},{"name":"Key Laboratory of Screening and Control of Infectious Diseases (Quanzhou Medical College), Fujian Provincial University","place":["Quanzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1016\/j.jhep.2017.11.039","article-title":"96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection","volume":"68","author":"Agarwal","year":"2018","journal-title":"J. Hepatol."},{"key":"B2","article-title":"Clinical significance of volume of distribution in pharmacotherapy","volume-title":"Statpearls (Internet).","author":"Bisht","year":"2026"},{"key":"B3","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1097\/QAD.0000000000002767","article-title":"Pharmacokinetics of tenofovir alafenamide with and without cobicistat in pregnant and postpartum women living with HIV","volume":"35","author":"Brooks","year":"2021","journal-title":"Aids"},{"key":"B4","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/S2468-1253(16)30107-8","article-title":"Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial","volume":"1","author":"Buti","year":"2016","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/S2468-1253(16)30024-3","article-title":"Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial","volume":"1","author":"Chan","year":"2016","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"997","DOI":"10.14218\/JCTH.2024.00237","article-title":"Anti-hepatitis B virus treatment with tenofovir amibufenamide has no impact on blood lipids: a real-world, prospective, 48-week Follow-up study","volume":"12","author":"Chen","year":"2024","journal-title":"J. Clin. Transl. Hepatol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.3760\/cma.j.cn501113-20221204-00607","volume":"30","year":"2022","journal-title":"Zhonghua Gan Zang Bing Za Zhi"},{"key":"B8","first-page":"376","article-title":"Drug interactions: a primer for the gastroenterologist","volume":"8","author":"Doligalski","year":"2012","journal-title":"Gastroenterol. Hepatol. (N Y)."},{"key":"B9","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1016\/j.jhep.2025.03.018","article-title":"EASL clinical practice guidelines on the management of hepatitis B virus infection","volume":"83","year":"2025","journal-title":"J. Hepatol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1124\/dmd.31.9.1108","article-title":"Multisite kinetic analysis of interactions between prototypical CYP3A4 subgroup substrates: Midazolam, testosterone, and nifedipine","volume":"31","author":"Galetin","year":"2003","journal-title":"Drug Metab. Dispos."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1093\/cid\/ciab763","article-title":"Pradefovir treatment in patients with chronic hepatitis B: week 24 results from a multicenter, double-blind, randomized, noninferiority, phase 2 trial","volume":"74","author":"Gao","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.14218\/JCTH.2022.00144","article-title":"IL-33 downregulates hepatic carboxylesterase 1 in acute liver injury via macrophage-derived exosomal miR-27b-3p","volume":"11","author":"Gao","year":"2023","journal-title":"J. Clin. Transl. Hepatol."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000001754","article-title":"A randomized, double-blind, phase 3, non-inferiority trial of pradefovir mesylate versus tenofovir disoproxil fumarate in Chinese patients with chronic hepatitis B","author":"Gao","year":"2026","journal-title":"Hepatology"},{"key":"B14","volume-title":"Adefovir dipivoxil [package insert]","author":"Gilead Sciences","year":"2012"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e1082","DOI":"10.1161\/CIR.0000000000000625","article-title":"AHA\/ACC\/AACVPR\/AAPA\/ABC\/ACPM\/ADA\/AGS\/APhA\/ASPC\/NLA\/PCNA guideline on the management of blood cholesterol: a report of the American college of cardiology\/american heart association task force on clinical practice guidelines","volume":"139","author":"Grundy","year":"2018","journal-title":"Circulation"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1165990","DOI":"10.3389\/fphar.2023.1165990","article-title":"Effectiveness and safety of tenofovir amibufenamide and its comparison with tenofovir alafenamide in patients with chronic hepatitis B: results from a retrospective real-world study","volume":"14","author":"Li","year":"2023","journal-title":"Front. Pharmacol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2926","DOI":"10.1128\/AAC.01566-05","article-title":"Metabolic activation of pradefovir by CYP3A4 and its potential as an inhibitor or inducer","volume":"50","author":"Lin","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"B18","doi-asserted-by":"publisher","first-page":"27369","DOI":"10.1038\/s41598-024-78656-0","article-title":"Comparison of lipid profile alterations in chronic hepatitis b patients receiving tenofovir alafenamide or tenofovir disoproxil fumarate","volume":"14","author":"Lin","year":"2024","journal-title":"Sci. Rep."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1134","DOI":"10.1111\/apt.16611","article-title":"Randomised clinical trial: 48 weeks of treatment with tenofovir amibufenamide versus tenofovir disoproxil fumarate for patients with chronic hepatitis B","volume":"54","author":"Liu","year":"2021","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B20","doi-asserted-by":"publisher","first-page":"649","DOI":"10.14218\/JCTH.2022.00058","article-title":"96-Week treatment of tenofovir amibufenamide and tenofovir disoproxil fumarate in chronic hepatitis B patients","volume":"11","author":"Liu","year":"2023","journal-title":"J. Clin. Transl. Hepatol."},{"key":"B21","volume-title":"Hepsera (Adefovir Dipivoxil): Summary of Product Characteristics","year":"2016"},{"key":"B22","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1111\/apt.70560","article-title":"Review article: renal safety profiles of tenofovir alafenamide, tenofovir disoproxil fumarate, and entecavir for the treatment of chronic hepatitis B infection-general and special populations","volume":"63","author":"Mak","year":"2026","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B23","doi-asserted-by":"publisher","first-page":"5907","DOI":"10.3748\/wjg.v29.i44.5907","article-title":"Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B: a real-world study","volume":"29","author":"Peng","year":"2023","journal-title":"World J. Gastroenterol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1097\/QAD.0000000000001744","article-title":"Plasma and intracellular pharmacokinetics of tenofovir in patients switched from tenofovir disoproxil fumarate to tenofovir alafenamide","volume":"32","author":"Podany","year":"2018","journal-title":"Aids"},{"key":"B25","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1021\/jm7012216","article-title":"Pradefovir: a prodrug that targets adefovir to the liver for the treatment of hepatitis B","volume":"51","author":"Reddy","year":"2008","journal-title":"J. Med. Chem."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e14029","DOI":"10.1111\/jvh.14029","article-title":"Efficacy and safety of tenofovir amibufenamide and tenofovir alafenamide for first-time HBV-related decompensated cirrhosis","volume":"32","author":"Rong","year":"2025","journal-title":"J. Viral Hepat."},{"key":"B27","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1161\/01.cir.0000437738.63853.7a","article-title":"ACC\/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American college of cardiology\/american heart association task force on practice guidelines","volume":"129","author":"Stone","year":"2013","journal-title":"Circulation"},{"key":"B28","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1002\/psp4.70010","article-title":"Evaluation of adefovir PBPK model to assess biomarker-informed OAT1 drug-drug interaction and effect of chronic kidney disease","volume":"14","author":"Tan","year":"2025","journal-title":"CPT Pharmacometrics Syst. Pharmacol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1002\/hep.29800","article-title":"Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance","volume":"67","author":"Terrault","year":"2018","journal-title":"Hepatology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"109285","DOI":"10.3748\/wjg.v31.i26.109285","article-title":"Tenofovir amibufenamide in chronic hepatitis B: lipid changes and 144-week safety with tenofovir disoproxil fumarate-to-tenofovir amibufenamide switch","volume":"31","author":"Zeng","year":"2025","journal-title":"World J. Gastroenterol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.intimp.2014.12.003","article-title":"Down-regulation of carboxylesterases 1 and 2 plays an important role in prodrug metabolism in immunological liver injury rats","volume":"24","author":"Zhang","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1053\/j.gastro.2009.08.063","article-title":"Hepatitis B virus resistance to nucleos(t)ide analogues","volume":"137","author":"Zoulim","year":"2009","journal-title":"Gastroenterology"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1862886\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T08:35:31Z","timestamp":1787560531000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1862886\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,24]]},"references-count":32,"alternative-id":["10.3389\/fphar.2026.1862886"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1862886","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,24]]},"article-number":"1862886"}}