title: Randomized comparison of tenofovir disoproxil fumarate vs emtricitabine and tenofovir disoproxil fumarate in patients with lamivudine-resistant chronic hepatitis B.
abstract: OBJECTIVE
  Tenofovir disoproxil fumarate (TDF) is active against lamivudine-resistant hepatitis B virus (HBV) infection, but data to support its clinical efficacy in this setting are limited.
  
  
  METHODS
  In a prospective, double-blind, 96-week trial, patients were randomly assigned (1:1) to groups given TDF (300 mg, n = 141) or a combination of emtricitabine (FTC, 200 mg; n = 139) and TDF (300 mg, FTC/TDF). Patients were hepatitis B e antigen (HBeAg)-positive or HBeAg-negative, with levels of HBV DNA ≥3 log10 IU/mL and lamivudine resistance mutations (HBV polymerase or reverse transcriptase amino acid substitutions rtM204I/V ± rtL180M by INNO-LiPA Multi-DR v3; Innogenetics, Inc, Alpharetta, GA). The primary end point was proportion with HBV DNA <69 IU/mL (Roche COBAS Taqman assay; Roche Molecular Systems, Inc, Pleasanton, CA).
  
  
  RESULTS
  Patient groups were well matched for demographic and disease characteristics, including region (60% from Europe), HBV genotype (45% genotype D), HBeAg status (47% HBeAg-positive), and duration of lamivudine treatment (mean, 3.8 years). At week 96 of treatment, 89.4% of patients in the TDF group and 86.3% in the FTC/TDF group had levels of HBV DNA <69 IU/mL (P = .43). HBeAg loss and seroconversion did not differ between groups; only 1 patient (0.7%) in the FTC/TDF group lost hepatitis B surface antigen. Treatment was well tolerated; confirmed renal events (creatinine increase of ≥0.5 mg/dL [>44 umol/L], creatinine clearance <50 mL/min, or level of PO4 <2 mg/dL [<0.65 mmol/L]) were generally mild and infrequent (<1%). Small reductions (<2%) in mean bone mineral density of hip and spine were detected by dual-energy x-ray absorptiometry in both groups. No TDF resistance developed through 96 weeks of treatment.
  
  
  CONCLUSIONS
  TDF alone is safe and effective for treatment of patients with lamivudine-resistant, chronic HBV infection. Clinical Trials.gov No, NCT00737568.
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: Scott.fung@uhn.on.ca.
authors.forename: Scott
authors.initials: S
authors.lastname: Fung
authors.affiliation: University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Kwan
authors.affiliation: Clinic for Infectious Diseases, Medical University of Novi Sad, Serbia.
authors.forename: Milotka
authors.initials: M
authors.lastname: Fabri
authors.affiliation: Medical University of Warsaw, Warsaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Horban
authors.affiliation: Clinic for Infectious and Tropical Diseases, Clinical Center of Serbia, Belgrade Medical Faculty, Belgrade, Serbia.
authors.forename: Mijomir
authors.initials: M
authors.lastname: Pelemis
authors.affiliation: Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Hie-Won
authors.initials: HW
authors.lastname: Hann
authors.affiliation: Uludag Universitesi Tip Fakultesi, Bursa, Gorukle, Turkey.
authors.forename: Selim
authors.initials: S
authors.lastname: Gurel
authors.affiliation: National Institute for Infectious Diseases, "Prof Dr Matei Bals," Bucharest, Romania.
authors.forename: Florin A
authors.initials: FA
authors.lastname: Caruntu
authors.affiliation: Gilead Sciences, Inc, Foster City, California.
authors.forename: John F
authors.initials: JF
authors.lastname: Flaherty
authors.affiliation: Gilead Sciences, Inc, Foster City, California.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Massetto
authors.affiliation: Gilead Sciences, Inc, Foster City, California.
authors.forename: Phillip
authors.initials: P
authors.lastname: Dinh
authors.affiliation: Gilead Sciences, Inc, Foster City, California.
authors.forename: Amoreena
authors.initials: A
authors.lastname: Corsa
authors.affiliation: Gilead Sciences, Inc, Foster City, California.
authors.forename: G Mani
authors.initials: GM
authors.lastname: Subramanian
authors.affiliation: Gilead Sciences, Inc, Foster City, California.
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.affiliation: University Hospital Brno and Faculty of Medicine, Masaryk University Brno, Brno, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Husa
authors.affiliation: Auckland City Hospital, Auckland, New Zealand.
authors.forename: Edward
authors.initials: E
authors.lastname: Gane
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004311:Double-Blind Method; D004338:Drug Combinations; D024882:Drug Resistance, Viral / Q000235:genetics; D000068679:Emtricitabine; D005060:Europe; D005260:Female; D005838:Genotype; 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 / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009520:New Zealand; D009656:North America; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D000068698:Tenofovir; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D004338:Drug Combinations; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D003841:Deoxycytidine; D019259:Lamivudine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine
keywords: HBV DNA; Hepatitis B e Antigen; Renal Function; Viral Suppression