title: Efficacy of switching to telbivudine plus adefovir in suboptimal responders to lamivudine plus adefovir.
abstract: OBJECTIVE
  To examine the efficacy of telbivudine (LdT) + adefovir (ADV) vs continuation of lamivudine (LAM) + ADV in patients with LAM-resistant chronic hepatitis B (CHB) who show a suboptimal response to LAM + ADV.
  
  
  METHODS
  This was a randomized, active-control, open-label, single-center, parallel trial. All eligible patients were enrolled in this study in Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea, between March 2010 and March 2011. Hepatitis Be antigen (HBeAg)-positive CHB patients whose serum hepatitis B virus (HBV) DNA remained detectable despite at least 6 mo of LAM + ADV therapy were included. Enrolled patients were randomized to either switching to LdT (600 mg/d orally) plus ADV (10 mg/d orally) (LdT + ADV group) or to continuation with LAM (100 mg/d orally) plus ADV (10 mg/d orally) (LAM + ADV group), and were followed for 48 wk. One hundred and six patients completed the 48-wk treatment period. Serum HBV DNA, HBeAg status, liver biochemistry and safety were monitored at baseline and week 12, 24, 36 and 48.
  
  
  RESULTS
  The duration of prior LAM + ADV treatment was 18.3 (LdT + ADV) and 14.9 mo (LAM + ADV), respectively (P = 0.131). No difference was seen in baseline serum HBV DNA between the two groups [3.66 (LdT + ADV) vs 3.76 (LAM + ADV) log10 IU/mL, P = 0.729]. At week 48, although there was no significant difference in the mean reduction of serum HBV DNA from baseline between LdT + ADV group and LAM + ADV group (-0.81 vs -0.47 log10 IU/mL, P = 0.167), more patients in the LdT + ADV group had undetectable HBV DNA levels compared to those in the LAM + ADV group (30.2% vs 11.5%, P = 0.019). Three patients with LdT + ADV treatment and 2 patients with LAM + ADV treatment achieved HBeAg loss. The patients in both groups tolerated the treatment well without serious adverse events. The proportion of patients with estimated glomerular filtration rate ≥ 90 mL/min per 1.73 m(2) in the LdT + ADV group increased from 49.1% (26/53) at baseline to 58.5% (31/53) at week 48, while that in the LAM + ADV group decreased from 37.7% (20/53) at baseline to 30.2% (16/53) at week 48.
  
  
  CONCLUSIONS
  The switch to LdT + ADV in suboptimal responders to LAM + ADV showed a significantly higher rate of virologic response at week 48. These results suggest that LdT + ADV could be a therapeutic option for patients who are unable to use enofovir disoproxil fumarate for any reason.
authors.affiliation: Hana Park, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si 463-712, South Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Park
authors.affiliation: Hana Park, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si 463-712, South Korea.
authors.forename: Jun Yong
authors.initials: JY
authors.lastname: Park
authors.affiliation: Hana Park, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si 463-712, South Korea.
authors.forename: Seung Up
authors.initials: SU
authors.lastname: Kim
authors.affiliation: Hana Park, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si 463-712, South Korea.
authors.forename: Do Young
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Hana Park, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si 463-712, South Korea.
authors.forename: Kwang-Hyub
authors.initials: KH
authors.lastname: Han
authors.affiliation: Hana Park, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si 463-712, South Korea.
authors.forename: Chae Yoon
authors.initials: CY
authors.lastname: Chon
authors.affiliation: Hana Park, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si 463-712, South Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ahn
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018579:Patient Selection; D011446:Prospective Studies; D056910:Republic of Korea; D000077712:Telbivudine; D013936:Thymidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D017211:Treatment Failure; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D000077712:Telbivudine; D019259:Lamivudine; C053001:adefovir; D000225:Adenine; D013936:Thymidine
keywords: Antiviral resistance; Chronic hepatitis B; Lamivudine; Suboptimal response; Telbivudine