{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T06:56:47Z","timestamp":1763535407800},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,12,22]],"date-time":"2016-12-22T00:00:00Z","timestamp":1482364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Multidrug\u2010resistant <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> continues to be an important clinical problem. The <jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content>\u2010109 study demonstrated that <jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content>\u00b1<jats:styled-content style=\"fixed-case\">LAM<\/jats:styled-content> is an effective salvage therapy through 96\u00a0weeks for <jats:styled-content style=\"fixed-case\">LAM<\/jats:styled-content>\u2010resistant patients who previously failed <jats:styled-content style=\"fixed-case\">ADV<\/jats:styled-content> add\u2010on or switch therapy. We evaluated the 5\u2010year efficacy and safety outcomes in patients receiving long\u2010term <jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content>\u00b1<jats:styled-content style=\"fixed-case\">LAM<\/jats:styled-content> in the <jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content>\u2010109 study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 59 patients completed the first phase of the <jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content>\u2010109 study and 54\/59 were rolled over into a long\u2010term prospective open\u2010label study of <jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content>\u00b1<jats:styled-content style=\"fixed-case\">LAM<\/jats:styled-content> 300\u00a0mg daily.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Results are reported at the end of year 5 of treatment. At year 5, 75% (45\/59) had achieved viral suppression by intent\u2010to\u2010treat analysis. Per\u2010protocol assessment revealed 83% (45\/54) were <jats:styled-content style=\"fixed-case\">HBV DNA<\/jats:styled-content> undetectable. Nine patients remained <jats:styled-content style=\"fixed-case\">HBV DNA<\/jats:styled-content> detectable, however 8\/9 had very low <jats:styled-content style=\"fixed-case\">HBV DNA<\/jats:styled-content> levels (&lt;264<jats:styled-content style=\"fixed-case\">IU<\/jats:styled-content>\/mL) and did not meet virological criteria for virological breakthrough (<jats:styled-content style=\"fixed-case\">VBT<\/jats:styled-content>). One patient experienced <jats:styled-content style=\"fixed-case\">VBT<\/jats:styled-content>, but this was in the setting of documented non\u2010compliance. The response was independent of baseline <jats:styled-content style=\"fixed-case\">LAM<\/jats:styled-content> therapy or mutations conferring <jats:styled-content style=\"fixed-case\">ADV<\/jats:styled-content> resistance. Four patients discontinued <jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content>, one patient was lost to follow\u2010up and one died from hepatocellular carcinoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Long\u2010term <jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content> treatment appears to be safe and effective in patients with prior failure of <jats:styled-content style=\"fixed-case\">LAM<\/jats:styled-content> and a suboptimal response to <jats:styled-content style=\"fixed-case\">ADV<\/jats:styled-content> therapy. These findings confirm that <jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content> has a high genetic barrier to resistance is active against multidrug\u2010resistant <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content>, and should be the preferred oral anti\u2010<jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> agent in <jats:styled-content style=\"fixed-case\">CHB<\/jats:styled-content> patients who fail treatment with <jats:styled-content style=\"fixed-case\">LAM<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ADV<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.13331","type":"journal-article","created":{"date-parts":[[2016,11,29]],"date-time":"2016-11-29T09:16:55Z","timestamp":1480411015000},"page":"827-835","source":"Crossref","is-referenced-by-count":14,"title":["Five\u2010year efficacy and safety of tenofovir\u2010based salvage therapy for patients with chronic hepatitis B who previously failed <scp>LAM<\/scp>\/<scp>ADV<\/scp> therapy"],"prefix":"10.1111","volume":"37","author":[{"given":"Lucy","family":"Lim","sequence":"first","affiliation":[{"name":"Liver Transplant &amp; Gastroenterology Department Austin Health  Melbourne VIC Australia"},{"name":"Gastroenterology Department St Vincent's Hospital  Melbourne VIC Australia"},{"name":"Molecular Research &amp; Development Laboratory Victorian Infectious Diseases Reference Laboratory  Melbourne VIC Australia"},{"name":"University of Melbourne  Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Thompson","sequence":"additional","affiliation":[{"name":"Gastroenterology Department St Vincent's Hospital  Melbourne VIC Australia"},{"name":"Molecular Research &amp; Development Laboratory Victorian Infectious Diseases Reference Laboratory  Melbourne VIC Australia"},{"name":"University of Melbourne  Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott","family":"Patterson","sequence":"additional","affiliation":[{"name":"Liver Transplant &amp; Gastroenterology Department Austin Health  Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"George","sequence":"additional","affiliation":[{"name":"Storr Liver Centre Westmead Millennium Institute for Medical Research Westmead Hospital &amp; University of Sydney  Sydney NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Strasser","sequence":"additional","affiliation":[{"name":"AW Morrow Gastroenterology &amp; Liver Centre Royal Prince Alfred Hospital  Camperdown NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Lee","sequence":"additional","affiliation":[{"name":"Gastroenterology Department Concord Hospital  Sydney NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Sievert","sequence":"additional","affiliation":[{"name":"Gastroenterology Department Monash Medical Centre  Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Nicoll","sequence":"additional","affiliation":[{"name":"Gastroenterology &amp; Hepatology Department Royal Melbourne Hospital  Melbourne VIC Australia"},{"name":"Gastroenterology Department Eastern Health  Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Desmond","sequence":"additional","affiliation":[{"name":"Gastroenterology Department St Vincent's Hospital  Melbourne VIC Australia"},{"name":"University of Melbourne  Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart","family":"Roberts","sequence":"additional","affiliation":[{"name":"Gastroenterology Department Alfred Hospital  Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaye","family":"Marion","sequence":"additional","affiliation":[{"name":"Mathematical &amp; 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