title: Efficacy of Tenofovir-based Rescue Therapy in Lamivudine-resistant Chronic Hepatitis B Patients With Failure of Lamivudine and Adefovir Combination.
abstract: OBJECTIVE
  In chronic hepatitis B patients, lamivudine (LAM) and adefovir (ADV) combination therapy is commonly used as a rescue therapy for LAM resistance, but it often results in incomplete viral suppression. We investigated the antiviral efficacy of tenofovir (TDF)/LAM combination therapy versus TDF monotherapy in LAM-resistant chronic hepatitis B (CHB) patients who failed to respond to LAM plus ADV rescue therapy.
  
  
  METHODS
  Among 108 patients with LAM-resistant CHB who had a partial virologic response (VR) to LAM and ADV combination therapy, Eighty one patients were finally included in this study.
  
  
  RESULTS
  Resistance to ADV (ADV-R) was present in 32 patients (39.5%), and the remaining 49 patients (60.5%) had a partial virologic response to LAM/ADV combination (ADV-P). The study subjects were treated with TDF alone (n=15) or TDF/LAM combination (n=66). VR was achieved in 61 patients (75.3%). The rates of VR at 6 and 12 months were not significantly different between TDF monotherapy and TDF/LAM combination therapy groups (46.7 vs. 68.2% at 6 months, and 66.7 vs. 75.9% at 12 months, log-rank P=0.357). Treatment efficacy of TDF alone or TDF/LAM combination was not statistically different according to pre-existing ADV or LAM resistant strains. In multivariate analysis, absolute HBV DNA levels at the start of TDF rescue treatment (P<0.001; OR, 0.556; 95% CI, 0.422-0.731) were the only significantly associated with VR.
  
  
  CONCLUSIONS
  TDF monotherapy was as effective as TDF/LAM combination therapy in maintaining viral suppression in patients with LAM-resistant patients who failed to respond to LAM/ADV combination therapy.
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea.
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea.
authors.forename: Seok Won
authors.initials: SW
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea; Biomedical Research Center, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea. Electronic address: nhpark@uuh.ulsan.kr.
authors.forename: Neung Hwa
authors.initials: NH
authors.lastname: Park
authors.affiliation: Biomedical Research Center, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea.
authors.forename: Bo Ryung
authors.initials: BR
authors.lastname: Park
authors.affiliation: Biomedical Research Center, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea.
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Biomedical Research Center, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea.
authors.forename: Chang Jae
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea.
authors.forename: Byung Uk
authors.initials: BU
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea.
authors.forename: In Du
authors.initials: ID
authors.lastname: Jeong
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea.
authors.forename: Byung Gyu
authors.initials: BG
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea.
authors.forename: Sung-Jo
authors.initials: SJ
authors.lastname: Bang
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea.
authors.forename: Jung Woo
authors.initials: JW
authors.lastname: Shin
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D019233:Retreatment; D000068698:Tenofovir / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D019259:Lamivudine; C053001:adefovir; D000068698:Tenofovir; D000225:Adenine
keywords: adefovir resistance; chronic hepatitis B; lamivudine resistance; tenofovir