title: Tenofovir is effective alone or with emtricitabine in adefovir-treated patients with chronic-hepatitis B virus infection.
abstract: OBJECTIVE
  We compared treatments for patients with chronic hepatitis B virus (HBV) infection who had an incomplete response to adefovir dipivoxil (ADV). We evaluated a combination of fixed-dose emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) from the start (early combination) versus TDF as monotherapy.
  
  
  METHODS
  Patients (n = 105) were randomly assigned to groups given TDF (n = 53) or FTC/TDF (n = 52). End points included HBV DNA suppression, biochemical and serologic response, and response by baseline or developed resistance mutations through 48 weeks of treatment. Patients given TDF monotherapy had the option to receive FTC, as fixed-dose FTC/TDF, if viremia persisted after week 24.
  
  
  RESULTS
  At baseline, patients' mean HBV DNA level was 5.97 log(10) copies/mL, and 58% had received lamivudine (LAM); LAM- and ADV-associated mutations were detected in 13 and 10 patients, respectively, by population sequencing and in 14 and 18 patients, respectively, by reverse hybridization line probe assay (INNO-LiPA HBV DR). Through week 24 (direct comparison of blinded therapy), viral decay curves were identical between groups. At week 48, 81% of patients initially given TDF or TDF/FTC had HBV DNA levels below 400 copies/mL. The presence of baseline LAM- or ADV-associated mutations did not affect response. Adherence to therapy appeared to be the primary factor associated with HBV DNA levels below 400 copies/mL at week 48.
  
  
  CONCLUSIONS
  TDF monotherapy and the combination of FTC and TDF had similar efficacy in patients with incomplete viral suppression after therapy with ADV; response was not influenced by the presence of baseline LAM- or ADV-associated mutations. Initial monotherapy followed by combination therapy was as effective as early combination therapy.
authors.affiliation: Universitätsklinik Leipzig, Leipzig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
authors.forename: Bernd
authors.initials: B
authors.lastname: Moller
authors.forename: Huy
authors.initials: H
authors.lastname: Trinh
authors.forename: Sing
authors.initials: S
authors.lastname: Chan
authors.forename: Emilio
authors.initials: E
authors.lastname: Suarez
authors.forename: Fabien
authors.initials: F
authors.lastname: Lavocat
authors.forename: Andrea
authors.initials: A
authors.lastname: Snow-Lampart
authors.forename: David
authors.initials: D
authors.lastname: Frederick
authors.forename: Jeff
authors.initials: J
authors.lastname: Sorbel
authors.forename: Katyna
authors.initials: K
authors.lastname: Borroto-Esoda
authors.forename: David
authors.initials: D
authors.lastname: Oldach
authors.forename: Franck
authors.initials: F
authors.lastname: Rousseau
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D000068698:Tenofovir
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000410:Alanine Transaminase; D000068679:Emtricitabine; D000225:Adenine; C106812:adefovir dipivoxil