title: Randomized, three-arm study to optimize lamivudine efficacy in hepatitis B e antigen-positive chronic hepatitis B patients.
abstract: OBJECTIVE
  Data about the efficacy of de novo combination therapies, or optimization strategy by adding the other drug based on the virological response at week 24 of low genetic barrier antiviral agents is still limited. This study aimed to compare the efficacy at week 104 of lamivudine monotherapy (MONO), lamivudine plus adefovir dipivoxil (ADV) combination therapy (COMBO), and lamivudine optimization strategy (OPTIMIZE).
  
  
  METHODS
  Adult patients without antiviral therapy within 6 months before screening with hepatitis B virus (HBV)-DNA ≥ 10(5) copies/mL, alanine aminotransferase 1.3-10 times upper limit of normal and compensated hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) were randomized into three groups with 1:1:1 ratio. Patients in OPTIMIZE group started with lamivudine 100 mg q.d., and ADV 10 mg q.d. was added to suboptimal responders (HBV-DNA > 1000 copies/mL at week 24) from week 30 to week 104, whereas patients with early virological response (HBV-DNA ≤ 1000 copies/mL at week 24) continued MONO until week 104. For all the patients receiving MONO, ADV would be added if virological breakthrough was confirmed.
  
  
  RESULTS
  At week 104, more patients in COMBO and OPTIMIZE groups achieved HBV-DNA < 300 copies/mL (53.3% [64/120] and 48.3% [58/120]), with less lamivudine resistance (0.8% and 6.7%) compared with MONO group (HBV-DNA < 300 copies/mL 34.8% [41/118], lamivudine resistance 58.5%). Patients under MONO with early virological response showed superior efficacy at week 104 (HBV-DNA < 300 copies/mL 73.1% [38/52], HBeAg seroconversion 40.4% [21/52]). All regimens were well tolerated.
  
  
  CONCLUSIONS
  Combination therapy of lamivudine plus ADV exhibited effective viral suppression and relatively low resistance in HBeAg-positive CHB patients. In lamivudine-treated patients with suboptimal virological response at week 24, promptly adding on ADV is necessary to prevent resistance development.
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Xieer
authors.initials: X
authors.lastname: Liang
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Sun
authors.forename: Xinyue
authors.initials: X
authors.lastname: Chen
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Jianning
authors.initials: J
authors.lastname: Jiang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Long
authors.forename: Hong
authors.initials: H
authors.lastname: Tang
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Yu
authors.forename: Jifang
authors.initials: J
authors.lastname: Sheng
authors.forename: Shijun
authors.initials: S
authors.lastname: Chen
authors.forename: Junqi
authors.initials: J
authors.lastname: Niu
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.forename: Junping
authors.initials: J
authors.lastname: Shi
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Dou
authors.forename: Mobin
authors.initials: M
authors.lastname: Wan
authors.forename: Jiaji
authors.initials: J
authors.lastname: Jiang
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.forename: Guangfeng
authors.initials: G
authors.lastname: Shi
authors.forename: Qin
authors.initials: Q
authors.lastname: Ning
authors.forename: Chengwei
authors.initials: C
authors.lastname: Chen
authors.forename: Deming
authors.initials: D
authors.lastname: Tan
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Jidong
authors.initials: J
authors.lastname: Jia
authors.forename: Hui
authors.initials: H
authors.lastname: Zhuang
authors.forename: Jinlin
authors.initials: J
authors.lastname: Hou
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D019259:Lamivudine; D000225:Adenine; C106812:adefovir dipivoxil
keywords: adefovir dipivoxil; hepatitis B e antigen; lamivudine; optimization strategy; virological response