title: Adding adefovir vs. switching to entecavir for lamivudine-resistant chronic hepatitis B (ACE study): a 2-year follow-up randomized controlled trial.
abstract: BACKGROUND
  Management of lamivudine-resistant chronic hepatitis B (CHB) remains challenging, as inappropriate choice of treatment may cause multidrug resistance. Until now, randomized trials directly comparing adding adefovir and switching to entecavir monotherapy have not been reported.
  
  
  OBJECTIVE
  This multicentre prospective randomized study was designed to compare the efficacy of these two strategies.
  
  
  METHODS
  Two hundred and nineteen lamivudine-resistant CHB patients were randomized to either adefovir-lamivudine combination group or entecavir monotherapy group (n = 110 vs. 109), and followed up for 24 months.
  
  
  RESULTS
  One hundred and eighty patients completed this study. At month 24, virological response rate [hepatitis B virus (HBV) DNA <60 IU/ml] was higher in the adefovir-lamivudine combination group compared with entecavir group (56.7% vs. 40%, P = 0.025), although biochemical and serological response rates were not significantly different. Genotypic resistance (9.2% vs. 24.6%, P = 0.005) and combined viral breakthrough (2.0% vs. 17.6%, P < 0.001) were more frequent in the entecavir group. However, by subgroup analysis, virological response rates were not significantly different between the two therapies in HBeAg-positive patients (44.9% vs. 35.7%, P = 0.268) or in patients with high baseline HBV DNA (≥7 log IU/ml) (40.7% vs. 31.3%, P = 0.320) at month 24.
  
  
  CONCLUSIONS
  This study showed that adefovir-lamivudine combination provides significantly higher antiviral efficacy and the lower resistance rate compared with the entecavir monotherapy in the management of lamivudine-resistant CHB. However, it had limited efficacy in HBeAg-positive patients or in patients with high baseline HBV DNA.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea.
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Yim
authors.forename: Yeon Seok
authors.initials: YS
authors.lastname: Seo
authors.forename: Eileen L
authors.initials: EL
authors.lastname: Yoon
authors.forename: Chang Wook
authors.initials: CW
authors.lastname: Kim
authors.forename: Chang Don
authors.initials: CD
authors.lastname: Lee
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Myung Seok
authors.initials: MS
authors.lastname: Lee
authors.forename: Choong Kee
authors.initials: CK
authors.lastname: Park
authors.forename: Hee Bok
authors.initials: HB
authors.lastname: Chae
authors.forename: Moon Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Soon Koo
authors.initials: SK
authors.lastname: Baik
authors.forename: Yun Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Jung Il
authors.initials: JI
authors.lastname: Lee
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Lee
authors.forename: Sun Pyo
authors.initials: SP
authors.lastname: Hong
authors.forename: Soon Ho
authors.initials: SH
authors.lastname: Um
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000328:Adult; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D005260:Female; D005500:Follow-Up Studies; D006147:Guanine / Q000031:analogs & derivatives; D006509:Hepatitis B / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D007118:Immunoassay; D019259:Lamivudine; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000235:genetics; D063065:Organophosphonates; D011446:Prospective Studies; D056910:Republic of Korea; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D009841:Oligonucleotides; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine