title: Long-term efficacy and safety of emtricitabine plus tenofovir DF vs. tenofovir DF monotherapy in adefovir-experienced chronic hepatitis B patients.
abstract: OBJECTIVE
  Suboptimal virologic response to nucleos(t)ide analogs may represent a significant risk factor for resistance development in patients with chronic hepatitis B virus infection; treatment options have not been well studied. We evaluated long-term efficacy and safety of tenofovir alone and in combination with emtricitabine in a prospective, placebo-controlled trial in patients who remained viremic on adefovir therapy.
  
  
  METHODS
  Hepatitis B e antigen-positive and -negative patients with hepatitis B virus DNA ⩾ 1000 copies/ml despite up to 96 weeks of adefovir were randomized to double-blind tenofovir or emtricitabine/tenofovir for 168 weeks. Patients with hepatitis B virus DNA ⩾ 400 copies/ml (⩾ 69IU/ml) at or after week 24 could switch to open-label emtricitabine/tenofovir.
  
  
  RESULTS
  Overall, 90/105 (86%) patients (46/53 tenofovir and 44/52 emtricitabine/tenofovir) completed the 168-week study period, including 74/105 (70%) patients (35/53 tenofovir and 39/52 emtricitabine/tenofovir) who completed the study on their initial randomized treatment. Long-term viral suppression (hepatitis B virus DNA <400 copies/ml) was maintained at week 168 in 84% and 82% of patients receiving either emtricitabine/tenofovir combination or tenofovir monotherapy, respectively (non-completer equal to failure analysis). Baseline viral load as well as the presence of lamivudine and/or adefovir resistance-associated mutations at baseline had no impact on long-term treatment response. No resistance to tenofovir was observed through 168 weeks. Both treatments had a favorable safety profile.
  
  
  CONCLUSIONS
  Tenofovir monotherapy is as effective as emtricitabine/tenofovir combination therapy in maintaining long-term viral suppression in patients with a suboptimal response to adefovir, and is well tolerated in this population.
authors.affiliation: Sektion Hepatologie, Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Universitätsklinikum Leipzig, Leipzig, Germany. Electronic address: thomas.berg@medizin.uni-leipzig.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.affiliation: INSERM U1052 and Hospices Civils de Lyon, Lyon, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
authors.affiliation: Private practice, Berlin, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Moeller
authors.affiliation: Private practice, San Jose, CA, USA.
authors.forename: Huy
authors.initials: H
authors.lastname: Trinh
authors.affiliation: Service d'Hepatologie and INSERM CRB3, University of Paris, Hopital Beaujon, Pavillon Abrami, Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.affiliation: Private practice, Flushing, NY, USA.
authors.forename: Sing
authors.initials: S
authors.lastname: Chan
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Kitrinos
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Dinh
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Flaherty
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover, Hannover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Manns
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004279:DNA, Viral / Q000097:blood; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D014766:Viremia / Q000188:drug therapy / Q000821:virology
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D063065:Organophosphonates; D003841:Deoxycytidine; C053001:adefovir; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine
keywords: Adefovir; Combination treatment; Emtricitabine; Hepatitis B; Monotherapy; Mutations; Resistance; Tenofovir