{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:20:10Z","timestamp":1790403610442,"version":"4.1.0"},"reference-count":57,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T00:00:00Z","timestamp":1593388800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000275","name":"Leverhulme Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000275","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013373","name":"NIHR Oxford Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["110110"],"award-info":[{"award-number":["110110"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns3:p>\n                    <ns3:bold>Background:<\/ns3:bold>\n                    Tenofovir (TFV) is a widely used treatment for chronic hepatitis B virus (HBV) infection. There is a high genetic barrier to the selection of TFV resistance-associated mutations (RAMs), but the distribution and clinical significance of TFV RAMs are not well understood. We here present assimilated evidence for putative TFV RAMs with the aims of cataloguing and characterising mutations that have been reported, and starting to develop insights into mechanisms of resistance.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Methods:<\/ns3:bold>\n                    We carried out a systematic literature search in PubMed and Scopus to identify clinical,\n                    <ns3:italic>in vitro<\/ns3:italic>\n                    and\n                    <ns3:italic>in silico<\/ns3:italic>\n                    evidence of TFV resistance. We included peer-reviewed studies presenting original data regarding virological TFV breakthrough, using published methods to assess the quality of each study. We generated a list of RAMs that have been reported in association with TFV resistance, developing a \u2018long-list\u2019 (all reported RAMs) and a \u2018short-list\u2019 (a refined list supported by the most robust evidence). We assessed the potential functional and structural consequences by mapping onto the crystal structure for HIV reverse transcriptase (RT), as the structure of HBV RT has not been solved.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Results:<\/ns3:bold>\n                    We identified a \u2018long-list\u2019 of 37 putative TFV RAMs in HBV RT, occurring within and outside sites of enzyme activity, some of which can be mapped onto a homologous HIV RT structure. A \u2018short-list\u2019 of nine sites are supported by the most robust evidence. If clinically significant resistance arises, it is most likely to be in the context of suites of multiple RAMs. Other factors including adherence, viral load, HBeAg status, HIV coinfection and NA dosage may also influence viraemic suppression.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Conclusion:<\/ns3:bold>\n                    There is emerging evidence for polymorphisms that may reduce susceptibility to TVF. However, good correlation between viral sequence and treatment outcomes is currently lacking; further studies are essential to optimise individual treatment and public health approaches.\n                  <\/ns3:p>","DOI":"10.12688\/wellcomeopenres.15992.1","type":"journal-article","created":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T07:10:15Z","timestamp":1593414615000},"page":"151","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":32,"title":["Hepatitis B virus resistance to tenofovir: fact or fiction? A systematic literature review and structural analysis of drug resistance mechanisms"],"prefix":"10.12688","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8398-0689","authenticated-orcid":false,"given":"Jolynne","family":"Mokaya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7436-8727","authenticated-orcid":false,"given":"Anna L.","family":"McNaughton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip A","family":"Bester","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Goedhals","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Barnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1937-4091","authenticated-orcid":false,"given":"Brian D","family":"Marsden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4036-4269","authenticated-orcid":false,"given":"Philippa 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Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-151\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-151\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-151\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T15:50:43Z","timestamp":1667145043000},"score":1,"resource":{"primary":{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-151\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,29]]},"references-count":57,"URL":"https:\/\/doi.org\/10.12688\/wellcomeopenres.15992.1","relation":{"has-review":[{"id-type":"doi","id":"10.21956\/wellcomeopenres.17540.r41653","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.17540.r43247","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.17540.r43245","asserted-by":"object"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.17540.r41653","asserted-by":"object"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.17540.r43247","asserted-by":"object"}]},"ISSN":["2398-502X"],"issn-type":[{"value":"2398-502X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,29]]},"assertion":[{"value":"Indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-151\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.17540.r41653, Dongping Xu, Institute of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital (Beijing 302 Hospital), Beijing, China, 16 Dec 2020, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-151\/v1#referee-response-41653","order":0,"name":"referee-response-41653","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.17540.r43247, Azwidowi Lukhwareni, Department of Medical Virology, University of Pretoria and National Health Laboratory Service, Tshwane Academic Division, Pretoria, South Africa, 08 Apr 2021, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-151\/v1#referee-response-43247","order":1,"name":"referee-response-43247","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by the Wellcome Trust [110110; to PCM], the Leverhulme Mandela Rhodes Scholarship to JM, the Medical Research Council UK to EB, the Oxford NIHR Biomedical Research Centre to EB. EB is an NIHR Senior Investigator. The views expressed in this article are those of the author and not necessarily those of the NHS, the NIHR, or the Department of Health. ALM is funded through NIHR Research Capability Funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}