{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,4,2]],"date-time":"2022-04-02T14:25:44Z","timestamp":1648909544454},"reference-count":0,"publisher":"Journal of Infection in Developing Countries","issue":"01","license":[{"start":{"date-parts":[[2021,1,31]],"date-time":"2021-01-31T00:00:00Z","timestamp":1612051200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Infect Dev Ctries"],"abstract":"<jats:p>Introduction: Adefovir plus entecavir (ADV+ETV) rescue therapy in ETV-resistant patients with chronic hepatitis B virus (HBV) infection is suboptimal in some patients. This study aims to elucidate the evolutionary characteristics of drug-resistant HBV mutants and their association with clinical responses in such patients.&#x0D;\nMethodology: Thirty-seven ETV-resistant patients were enrolled, among whom twelve had an inadequate virological response to ADV+ETV rescue therapy. The clonal sequence (\u00b3 20 clones\/sample) of HBV reverse transcriptase gene was performed to identify the resistance mutations. Phenotypic analysis was performed to evaluate the replication capacity and drug susceptibility of the mutants.&#x0D;\nResults: ETV-resistant mutants were continuously detected in 10 of the 12 patients, and multidrug-resistant (MDR) mutants, including a novel strain (rtL180M+A181V+T184A+S202G+M204V), were detected in two patients. Seven of the 12 patients who subsequently received tenofovir (TDF)-based therapy for 38 (23\u221260) months all achieved undetectable HBV DNA after treatment, and ETV-resistant mutants converted to wild-type in the four patients\u2019 samples. In contrast, the other five patients who did not achieve an adequate virological response had remaining of ETV-resistant mutants. The novel MDR strain exhibited multiple resistances to LAM, ADV, and ETV, and 11.2-fold lower susceptibility to TDF.&#x0D;\nConclusions: This study is the first to demonstrate that MDR HBV mutations may contribute to the poor efficacy of ADV+ETV combination therapy in ETV-resistant patients. Moreover, a novel MDR HBV strain was identified. Our results indicate that a TDF-based rescue therapy would be effective for the treatment of the refractory cases.<\/jats:p>","DOI":"10.3855\/jidc.12643","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T20:39:30Z","timestamp":1612989570000},"page":"131-140","source":"Crossref","is-referenced-by-count":0,"title":["Multiple drug-resistant HBV mutation may contribute to poor response of adefovir + entecavir in entecavir-resistant patients"],"prefix":"10.3855","volume":"15","author":[{"given":"Jinman","family":"Shao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Ming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rongjuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Le","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongping","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2222","published-online":{"date-parts":[[2021,1,31]]},"container-title":["The Journal of Infection in Developing Countries"],"original-title":[],"link":[{"URL":"https:\/\/www.jidc.org\/index.php\/journal\/article\/download\/12643\/2446","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.jidc.org\/index.php\/journal\/article\/download\/12643\/2446","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T20:39:30Z","timestamp":1612989570000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jidc.org\/index.php\/journal\/article\/view\/12643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,31]]},"references-count":0,"journal-issue":{"issue":"01","published-online":{"date-parts":[[2021,1,31]]}},"URL":"https:\/\/doi.org\/10.3855\/jidc.12643","relation":{},"ISSN":["1972-2680"],"issn-type":[{"value":"1972-2680","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,31]]}}}