Activity of adefovir dipivoxil against all patterns of lamivudine-resistant hepatitis B viruses in patients.
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 > 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.
Westland
C E
CE
Gilead Sciences, Inc., Foster City, CA, USA.
Yang
H
H
Delaney
W E
WE
Wulfsohn
M
M
Lama
N
N
Gibbs
C S
CS
Miller
M D
MD
Fry
J
J
Brosgart
C L
CL
Schiff
E R
ER
Xiong
S
S
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D015684:Gene Products, pol / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000627:therapeutic use*; D011517:Prothrombin Time; D012709:Serum Albumin / Q000032:analysis; D019562:Viral Load
D000998:Antiviral Agents; D015684:Gene Products, pol; D063065:Organophosphonates; C066027:P protein, Hepatitis B virus; D012709:Serum Albumin; D019259:Lamivudine; D000410:Alanine Transaminase; D000225:Adenine; C106812:adefovir dipivoxil