Increased risk of adefovir resistance in patients with lamivudine-resistant chronic hepatitis B after 48 weeks of adefovir dipivoxil monotherapy.
Although adefovir dipivoxil (ADV) has a unique profile of delayed and infrequent resistance in treatment-naïve chronic hepatitis B patients, the association of ADV resistance with previous lamivudine (LAM) resistance is not well understood. We compared the emergence of the ADV-resistant mutations rtA181V/T and rtN236T between LAM-resistant patients and treatment-naïve patients at 48 weeks of ADV monotherapy. Fifty-seven LAM-resistant patients and 38 treatment-naïve patients were treated with 10 mg/d ADV for more than 48 weeks. Both baseline and 48-week blood samples were analyzed for ADV-resistant mutations via restriction fragment mass polymorphism analysis. Antiviral responses were evaluated according to changes in serum HBV DNA (measured via real-time polymerase chain reaction) and alanine aminotransferase (ALT) levels and loss of hepatitis B e antigen (HBeAg). After 48 weeks, 10 (18%) of the 57 LAM-resistant patients were found to have developed ADV-resistant mutations, whereas none of the 38 treatment-naïve patients developed such mutations (P < .01). Among LAM-resistant patients, the reduction in serum HBV DNA levels was significantly lower in patients with ADV-resistant mutations than in those without such mutations (-1.04 vs. -2.63 log10 copies/mL) (P = .01). However, the rates of serum ALT normalization (60% vs. 55%) and HBeAg loss (14% vs. 21%) were not significantly different between the 2 groups (P > .05). In conclusion, the emergence of the rtA181V/T and rtN236T mutations was more common in LAM-resistant patients than in treatment-naïve patients after 48 weeks of ADV therapy and was associated with reduced antiviral efficacy to drug treatment.
Lee
Yoon-Seon
YS
Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Suh
Dong Jin
DJ
Lim
Young-Suk
YS
Jung
Suk Won
SW
Kim
Kang Mo
KM
Lee
Han Chu
HC
Chung
Young-Hwa
YH
Lee
Yung Sang
YS
Yoo
Wangdon
W
Kim
Soo-Ok
SO
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D001483:Base Sequence; D016022:Case-Control Studies; D004279:DNA, Viral / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005260:Female; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D063065:Organophosphonates / Q000008:administration & dosage*; D010597:Pharmacogenetics; D011336:Probability; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; D000225:Adenine; C106812:adefovir dipivoxil