Skip to main content

Association of preexisting drug-resistance mutations and treatment failure in hepatitis B patients.

Publication ,  Journal Article
Ma, J; Zhang, Y; Chen, X; Jin, Y; Chen, D; Wu, Y; Cui, J; Wang, H; Liu, J; Li, N; Gao, F
Published in: PLoS One
2013

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-naïve 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-naïve patients. Moreover, the low-frequency same linked LAMr mutations (<0.15%) were detected in 24% of the treatment-naïve 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 -naïve hepatitis B patients, and underline the importance of the detection of minority single and linked drug-resistance mutations before initiating antiviral therapy.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

7

Start / End Page

e67606

Location

United States

Related Subject Headings

  • Viral Load
  • Treatment Failure
  • Mutation
  • Humans
  • Hepatitis B virus
  • Hepatitis B
  • Genome, Viral
  • General Science & Technology
  • Drug Resistance, Viral
  • DNA Mutational Analysis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ma, J., Zhang, Y., Chen, X., Jin, Y., Chen, D., Wu, Y., … Gao, F. (2013). Association of preexisting drug-resistance mutations and treatment failure in hepatitis B patients. PLoS One, 8(7), e67606. https://doi.org/10.1371/journal.pone.0067606
Ma, Jie, Yingchun Zhang, Xinyue Chen, Yi Jin, Dexi Chen, Yun Wu, Jing Cui, et al. “Association of preexisting drug-resistance mutations and treatment failure in hepatitis B patients.PLoS One 8, no. 7 (2013): e67606. https://doi.org/10.1371/journal.pone.0067606.
Ma J, Zhang Y, Chen X, Jin Y, Chen D, Wu Y, et al. Association of preexisting drug-resistance mutations and treatment failure in hepatitis B patients. PLoS One. 2013;8(7):e67606.
Ma, Jie, et al. “Association of preexisting drug-resistance mutations and treatment failure in hepatitis B patients.PLoS One, vol. 8, no. 7, 2013, p. e67606. Pubmed, doi:10.1371/journal.pone.0067606.
Ma J, Zhang Y, Chen X, Jin Y, Chen D, Wu Y, Cui J, Wang H, Liu J, Li N, Gao F. Association of preexisting drug-resistance mutations and treatment failure in hepatitis B patients. PLoS One. 2013;8(7):e67606.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

7

Start / End Page

e67606

Location

United States

Related Subject Headings

  • Viral Load
  • Treatment Failure
  • Mutation
  • Humans
  • Hepatitis B virus
  • Hepatitis B
  • Genome, Viral
  • General Science & Technology
  • Drug Resistance, Viral
  • DNA Mutational Analysis