{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:49:54Z","timestamp":1791910194881,"version":"4.3.4"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,9,23]],"date-time":"2016-09-23T00:00:00Z","timestamp":1474588800000},"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":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>A major hurdle in the long\u2010term treatment of chronic hepatitis B (CHB) patients is to maintain viral suppression in the absence of drug resistance. To date, no evidence of resistance to tenofovir disoproxil fumarate (TDF) has been observed. A cumulative evaluation of CHB patients who qualified for resistance surveillance over 8\u00a0years of TDF treatment was conducted. Patients in studies GS\u2010US\u2010174\u20100102 (HBeAg\u2212) and GS\u2010US\u2010174\u20100103 (HBeAg+) were randomized 2:1 to receive TDF or adefovir dipivoxil (ADV) for 48\u00a0weeks followed by open\u2010label TDF through year 8. Population sequencing of HBV pol\/RT was attempted for all TDF\u2010treated patients at baseline and, annually if viremic, at discontinuation, or with addition of emtricitabine. Overall, 88\/641 (13.7%) patients qualified for sequence analysis at one or more time points. The percentage of patients qualifying for sequence analysis declined over time, from 9 to 11% in years 1\u20102 to &lt;4% over years 3\u20108. Forty\u2010one episodes of virologic breakthrough (VB) occurred throughout the study, with most (<jats:italic>n<\/jats:italic>=29, 70%) associated with nonadherence to study medication. Fifty\u2010nine per cent of VB patients with an opportunity to resuppress HBV achieved HBV DNA resuppression. A minority of patients who qualified for sequencing had polymorphic (41\/165, 24.8%) or conserved (17\/165, 10.3%) site changes in pol\/RT, with six patients developing lamivudine and\/or ADV resistance\u2010associated mutations. No accumulation of conserved site changes was detected. The long\u2010term treatment of CHB with TDF monotherapy maintains effective suppression of HBV DNA through 8\u00a0years, with no evidence of TDF resistance or accumulation of conserved site changes.<\/jats:p>","DOI":"10.1111\/jvh.12613","type":"journal-article","created":{"date-parts":[[2016,9,23]],"date-time":"2016-09-23T11:25:21Z","timestamp":1474629921000},"page":"68-74","source":"Crossref","is-referenced-by-count":112,"title":["No detectable resistance to tenofovir disoproxil fumarate in HBeAg+ and HBeAg\u2212 patients with chronic hepatitis B after 8\u00a0years of treatment"],"prefix":"10.1111","volume":"24","author":[{"given":"Y.","family":"Liu","sequence":"first","affiliation":[{"name":"Gilead Sciences, Inc  Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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J.","family":"Gane","sequence":"additional","affiliation":[{"name":"Auckland City Hospital  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,9,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200205303462202"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2003.09.033"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.09.020"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22414"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.10.026"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22841"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24318"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26686"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-014-3486-7"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-308353"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.11.024"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.12.028"},{"key":"e_1_2_7_14_1","unstructured":"LiuY MitchellB DinhP MillerMD KitrinosKM eds.Antiviral Activity of Tenofovir Alafenamide Against Drug\u2010Resistant HBV Isolates In Vitro [Poster 2021].San Francisco CA:American Association for the Study of Liver Diseases (AASLD);201513\u201017 November."},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0802878"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24078"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26277"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.07.019"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl092"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.293.7.817"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1086\/498025"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-133-1-200007040-00004"},{"key":"e_1_2_7_23_1","unstructured":"KoksalI SonmezS eds.The relationship between patient's adherence to antiviral therapy and virological response in chronic hepatitis B and hepatitis C: Results of a 48\u2010week observational study [Abstract].San Francisco CA:American Association for the Study of Liver Diseases (AASLD);201513\u201017 November."},{"key":"e_1_2_7_24_1","unstructured":"AbreuRM Paranagua\u2010VezozzoD CarrilhoFJ et\u00a0al. eds.Four years real\u2010life experience with antiviral adherence in chronic hepatitis B infection in a tertiary university hospital [Abstract].San Francisco CA:American Association for the Study of Liver Diseases (AASLD);201513\u201017 November."},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2006.00647.x"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.11.016"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0089789"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-015-3960-x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2010.223206"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2014.05.024"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23246"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2007.06.011"}],"container-title":["Journal of Viral Hepatitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvh.12613","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvh.12613","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.12613","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T14:43:45Z","timestamp":1696171425000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvh.12613"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9,23]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,1]]}},"alternative-id":["10.1111\/jvh.12613"],"URL":"https:\/\/doi.org\/10.1111\/jvh.12613","archive":["Portico"],"relation":{},"ISSN":["1352-0504","1365-2893"],"issn-type":[{"value":"1352-0504","type":"print"},{"value":"1365-2893","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9,23]]}}}