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Pre‐existing YMDD mutants in treatment‐naïve patients with chronic hepatitis B are not selected during lamivudine therapy
Author(s) -
Lee Sae Hwan,
Kim Hong Soo,
Byun InSeon,
Jeong Soung Won,
Kim Sang Gyune,
Jang Jae Young,
Kim Young Seok,
Kim Boo Sung
Publication year - 2012
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.23191
Subject(s) - lamivudine , virology , mutant , medicine , reverse transcriptase , hepatitis b virus , mutation , microbiology and biotechnology , virus , polymerase chain reaction , biology , gene , genetics
Abstract Although the rate at which mutations in the tyrosine‐methionine‐aspartate‐aspartate (YMDD) motif of hepatitis B virus polymerase form is high during prolonged lamivudine (LAM) therapy, these mutations sometimes occur naturally in treatment‐naïve patients with chronic hepatitis B. The prevalence of natural YMDD mutants differs geographically, and its clinical significance during LAM therapy is unknown. This study aimed to investigate whether pre‐existing YMDD mutants were selected during LAM therapy. It included 14 treatment‐naïve patients who were treated with LAM for at least 9 months. LAM resistance was evaluated before and at 3‐month intervals during treatment. Mutations were analyzed by direct sequencing, restriction fragment mass polymorphism (RFMP) assays, and a single‐step multiplex polymerase chain reaction (PCR) test using dual‐priming oligonucleotide (DPO) primers. DPO‐based multiplex PCR showed two YMDD mutations in two patients before LAM therapy; rtM204V and rtL180M + rtM204V/I. Further, two patients had an rtL180M mutation without an accompanying rtM204V/I mutation. No mutant was detected in any patient by direct sequencing or the RFMP assay before LAM therapy. A virological response was observed at 3 months in all patients with pre‐existing YMDD mutants. All mutations disappeared after 3 months of LAM therapy, and during the follow‐up period, no re‐emergence was detected by any of the three methods. Further, the viral load was suppressed optimally. In conclusion, pre‐existing YMDD mutants were cleared early during the course of LAM therapy, which produced a consistent virological response, and the mutants were not selected by LAM therapy. J. Med. Virol. 84:217–222, 2012. © 2011 Wiley Periodicals, Inc.