Early changes of hepatitis B virus quasispecies during lamivudine treatment and the correlation with antiviral efficacy.
OBJECTIVE
To investigate dynamic changes of hepatitis B virus (HBV) quasispecies within the reverse transcriptase (RT) region during the early stage of lamivudine treatment and the correlation with antiviral efficacy.


METHODS
Twenty-five chronic hepatitis B patients received lamivudine treatment for 48 weeks. Fourteen patients responded to lamivudine, while eleven patients were non-responders. HBV DNA was extracted from serum samples at baseline and week 4. The RT region of HBV was amplified, then cloned and sequenced. Quasispecies complexity and diversity within the RT region were analyzed at baseline and week 4, and viral nucleotide substitution rates during the first 4 weeks were calculated.


RESULTS
The quasispecies complexity and diversity were not different between responders and non-responders at baseline (p>0.05). However, the quasispecies complexity and diversity of responders were significantly lower than those of non-responders at week 4 (p<0.01). Furthermore, the viral nucleotide substitution rate of responders was significantly higher than that of non-responders (p<0.05).


CONCLUSIONS
The dynamic changes of HBV quasispecies within the RT region showed distinct patterns between responders and non-responders during early stage of lamivudine treatment. The dynamic changes of quasispecies complexity and diversity during the first 4 weeks were correlated with lamivudine antiviral efficacy and antiviral resistance.
Chen
Li
L
Department of Infectious Disease, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Zhang
Qian
Q
Yu
De-min
DM
Wan
Mo-bin
MB
Zhang
Xin-xin
XX
D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D016896:Treatment Outcome
D000998:Antiviral Agents; D004279:DNA, Viral; D019259:Lamivudine; D012194:RNA-Directed DNA Polymerase