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学科主题基础医学
Association of Preexisting Drug-Resistance Mutations and Treatment Failure in Hepatitis B Patients
Ma, Jie1,2; Zhang, Yingchun2; Chen, Xinyue3; Jin, Yi3; Chen, Dexi1; Wu, Yun2; Cui, Jing2; Wang, Haitao2; Liu, Jia5; Li, Ning1,3,4; Gao, Feng6
刊名PLOS ONE
2013-07-30
DOI10.1371/journal.pone.0067606
8期:7
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]REPLICATION IN-VITRO ; LAMIVUDINE THERAPY ; VIRUS POLYMERASE ; NAIVE PATIENTS ; YMDD-MOTIF ; INFECTION ; HBV ; POPULATIONS ; HIV ; RECOMMENDATIONS
英文摘要

The role of preexisting minority drug-resistance mutations in treatment failure has not been fully understood in chronic hepatitis B patients. To understand mechanisms of drug resistance, we analyzed drug-resistance mutations in 46 treatment-failure patients and in 29 treatment-naive patients and determined linkage patterns of the drug-resistance mutations in individual viral genomes using a highly sensitive parallel allele-specific sequencing (PASS) method. Lamivudine resistance (LAMr) mutations were predominant in treatment-failure patients, irrespective of the inclusion of LAM in the regimen. The primary LAMr mutations M204V and M204I were detected in 100% and 30% of the treatment-failure patients, respectively. Two secondary LAMr mutations (L180M and V173L) were also found in most treatment-failure patients (87% and 78%, respectively). The linkages containing these three mutations dominated the resistant viruses. Importantly, minority LAMr mutations present in < 2% of the viral population were detected in 83% of the treatment-naive patients. Moreover, the low-frequency same linked LAMr mutations (< 0.15%) were detected in 24% of the treatment-naive patients. Our results demonstrate that the selection of preexisting minority linked LAMr mutations may be an important mechanism for the rapid development of LAM resistance, caution the continuous use of LAM to treat drug-experienced and -naive hepatitis B patients, and underline the importance of the detection of minority single and linked drug-resistance mutations before initiating antiviral therapy.

语种英语
WOS记录号WOS:000323114200004
资助机构China Primary Health Care Foundation
引用统计
被引频次:4[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63221
专题北京大学基础医学院_病原生物学系
北京大学第一临床医学院_神经内科
作者单位1.Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA
2.Beijing Inst Liver Dis, Beijing, Peoples R China
3.Beijing Baihuirui Biotechnol Inc, Beijing, Peoples R China
4.Capital Med Univ, Beijing Youan Hosp, Dept Med, Beijing, Peoples R China
5.Capital Med Univ, Beijing Youan Hosp, Dept Surg, Beijing, Peoples R China
6.Peking Univ, Hlth Sci Ctr, Dept Microbiol, Beijing 100871, Peoples R China
推荐引用方式
GB/T 7714
Ma, Jie,Zhang, Yingchun,Chen, Xinyue,et al. Association of Preexisting Drug-Resistance Mutations and Treatment Failure in Hepatitis B Patients[J]. PLOS ONE,2013,8(7).
APA Ma, Jie.,Zhang, Yingchun.,Chen, Xinyue.,Jin, Yi.,Chen, Dexi.,...&Gao, Feng.(2013).Association of Preexisting Drug-Resistance Mutations and Treatment Failure in Hepatitis B Patients.PLOS ONE,8(7).
MLA Ma, Jie,et al."Association of Preexisting Drug-Resistance Mutations and Treatment Failure in Hepatitis B Patients".PLOS ONE 8.7(2013).
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