Changes in viral loads of lamivudine-resistant mutants during entecavir therapy.
OBJECTIVE
Entecavir therapy is effective against lamivudine-resistant virus in patients with hepatitis B virus infection. We investigated viral load changes of YMDD mutant virus (rtM204I [YIDD sequence], rtM204V [YVDD]) in serial serum samples during entecavir treatment for lamivudine-resistant virus and determined changes in viral precore and core promoter mutants.


METHODS
Nineteen patients were treated in randomized, double-blind phase II clinical trials of entecavir at 0.5 or 1.0 mg for breakthrough hepatitis due to lamivudine-resistant virus. Viral changes in YMDD mutants (rtM204I, rtM204V), amino acid changes in the polymerase reverse transcriptase region and precore/core promoter mutations at 52 weeks were determined in 18 patients.


RESULTS
Changes in viral loads of rtM204I and rtM204V were similar. No differences in load changes were seen betweenthe 0.5 and 1.0 mg groups. However, load changes for rtM204I alone were greater than those for the rtM204I + rtM204V mixed-type (P = 0.042, at both 40 and 52 weeks). Load changes in rtM204I and rtM204V with G1896A tended to be greater than those without. Moreover, G1896A was replaced by wild-type virus in two patients at 52 weeks.


CONCLUSIONS
RtM204I only or the existence of precore mutation was more sensitive to entecavir therapy against lamivudine-resistant virus.
Suzuki
Fumitaka
F
Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
Suzuki
Yoshiyuki
Y
Akuta
Norio
N
Yatsuji
Hiromi
H
Sezaki
Hitomi
H
Arase
Yasuji
Y
Kawamura
Yusuke
Y
Hosaka
Tetsuya
T
Kobayashi
Masahiro
M
Ikeda
Kenji
K
Kobayashi
Mariko
M
Watahiki
Sachiyo
S
Kumada
Hiromitsu
H