Activity of adefovir dipivoxil against all patterns of lamivudine-resistant hepa

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J Viral Hepat. 2005 Jan;12(1):67-73.

Activity of adefovir dipivoxil against all patterns of lamivudine-resistant

hepatitis B viruses in patients.

Westland CE, Yang H, Delaney WE 4th, Wulfsohn M, Lama N, Gibbs CS,

MD, Fry J, Brosgart CL, Schiff ER, Xiong S.

Gilead Sciences, Inc., City, CA, USA.

Summary. One hundred and thirty-one post-liver transplantation patients with

chronic hepatitis B and failing lamivudine therapy with detectable serum

hepatitis B virus (HBV) deoxyribonucleic acid by hybridization assays or

>/=1 x 10(6) copies/mL by polymerase chain reaction, and elevated alanine

transaminase levels despite continuous lamivudine, were enrolled in an

open-label study of adefovir dipivoxil. 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.

PMID: 15655050 [PubMed - in process]

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