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Activity of Adefovir Dipivoxil Against All Patterns of Lamivudine-resistant
Hepatitis B Virus
In
an open-label study of adefovir dipivoxil (Hepsera), researchers studied one hundred and thirty-one
post-liver transplantation
patients
with chronic hepatitis B and failing lamivudine (Epivir-HBV)
therapy with detectable serum
hepatitis B virus (HBV) deoxyribonucleic acid by hybridization assays
or >/=1 × 106 copies/mL by polymerase chain reaction, and elevated
alanine transaminase levels despite continuous lamivudine.
The
B and C domains of HBV polymerase were sequenced for baseline samples
to determine the presence of lamivudine resistance mutations.
The
results showed that 98% of the samples had tyrosine-methionine-aspartate-aspartate
(YMDD) mutations, indicating a strong correlation between the above
clinical definition of lamivudine treatment failure and the presence
of YMDD
mutations.
In
addition to the rtM204V/I and the rtL180M mutations, the mutation
rtV173L was identified in 19% of patients.
Four
major patterns of lamivudine-resistant HBV were identified: rtL180M
+ rtM204V (60%), rtV173L + rtL180M + rtM204V (19%), rtM204I (9%)
and rtL180M + rtM204I (9%).
Treatment
with adefovir dipivoxil showed similar antiviral efficacy in patients
with lamivudine-resistant
virus
from all four patterns.
Gilead
Sciences, Inc., Foster City, CA; and Division of Hepatology University
of Miami, Miami, FL, USA.
02/16/05
Reference
C
E Westland and others. Activity of Adefovir Dipivoxil
Against All Patterns of Lamivudine-Resistant Hepatitis B Viruses
in Patients. Journal of Viral Hepatitis 12(1): 67-73,
2005.
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