[Resistance mutation patterns of hepatitis B virus in patients with suboptimal response to adefovir dipivoxil therapy after lamivudine resistance].
OBJECTIVE
To investigate the resistance mutation patterns of hepatitis B virus(HBV) during adefovir dipivoxil (ADV) monotherapy or combination therapy after lamivudine(LAM) resistance.


METHODS
Serum samples from fifteen patients with suboptimal viral response to ADV therapy after LAM resistance were collected. The RT region of HBV P gene was PCR-applied, cloned and sequenced, and the mutation patterns in relation to resistance were analyzed.


RESULTS
The ADV resistance mutation patterns of A181T+N236T, A181V, A181T were selected in ADV monotherapy group. The LAM resistance mutation patterns of M204V+L180M, M204V+L180M+L229V, M204I+L80I, M204V+L180M+V207I were detected in the combination therapy group. 20% of clones from three serum samples were detected double resistance to LAM and entecavir (ETV) in the combination therapy group, the resistance patterns were M204I+L80I+T184I (2/10), M204V+L180M+T184S (2/10), and M204V+L180M+G173L+S202G (2/10) respectively. I269L clones were detected in two serum samples from both two groups and P109S clones also detected in the one from monotherapy group.


CONCLUSIONS
In the patients with suboptimal viral response to ADV therapy after LAM resistance, the ADV resistance mutation patterns of A181T+N236T, A181V and A181T could easily be selected during ADV monotherapy; while in the patients with combination therapy, the LAM resistance mutation patterns of M204V+L180M, M204V+L180M+L229V, M204I+L80I, and M204V+L180M+V207I were predominant, the ETV resistance mutation T184I/S and S202G could be selected. The mutation patterns of I269L and P109S may impact the responses to ADV therapy in some patients.
Wu
Zhen-ping
ZP
Third Central Hospital, Tianjin Medical University, Tianjin 300170, China.
Hang
Tao
T
Gao
Ying-tang
YT
Li
Ying
Y
Liu
Tong
T
Jing
Li
L
Liu
Lei
L
Du
Zhi
Z
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics*; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy / Q000821:virology*; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000494:pharmacology / Q000627:therapeutic use*
D000998:Antiviral Agents; D063065:Organophosphonates; D019259:Lamivudine; D000225:Adenine; C106812:adefovir dipivoxil