title: Tenofovir disoproxil fumarate (TDF) vs. emtricitabine (FTC)/TDF in lamivudine resistant hepatitis B: A 5-year randomised study.
abstract: Long-term treatment with tenofovir disoproxil fumarate (TDF) alone, or in combination with emtricitabine (FTC) is associated with sustained viral suppression in patients with lamivudine resistant (LAM-R) chronic hepatitis B (CHB).
  
  
  
  LAM-R CHB patients were randomised 1:1 to receive TDF 300mg or FTC 200mg and TDF 300mg once daily in a prospective, double blind, study. The proportion of patients with plasma hepatitis B virus (HBV) DNA<69IU/ml (<400copies/ml) at week 96 (primary efficacy endpoint) was reported previously. Here we present week 240 follow-up data.
  
  
  
  Overall, 280 patients were randomised to receive TDF (n=141) or FTC/TDF (n=139), and 85.4% completed 240weeks of treatment. At week 240, 83.0% of patients in the TDF arm, and 82.7% of patients in the FTC/TDF treatment arm had HBV DNA<69IU/ml (p=0.96). Rates of normal alanine aminotransferase (ALT) and normalised ALT were similar between groups (p=0.41 and p=0.97 respectively). Hepatitis B e antigen loss and seroconversion at week 240 were similar between groups, (p=0.41 and p=0.67 respectively). Overall, six patients achieved hepatitis B surface antigen (HBsAg) loss and one patient (FTC/TDF arm) had HBsAg seroconversion by week 240. No TDF resistance was observed up to week 240. Treatment was generally well tolerated, and renal events were mild and infrequent (∼8.6%). The mean change in bone mineral density at week 240 was -0.98% and -2.54% at the spine and hip, respectively.
  
  
  
  TDF monotherapy was effective and well tolerated in LAM-R CHB patients for up to 240weeks.
  
  
  
  The goal of oral antiviral treatment for chronic hepatitis B (CHB) is to achieve and maintain undetectable HBV DNA levels. Treatment options with enhanced potency, and low risk of resistance development for patients infected with lamivudine resistant (LAM-R) HBV are required. Tenofovir disoproxil fumarate (TDF) monotherapy was effective and well tolerated without TDF resistance development in CHB patients with LAM-R, for up to 240weeks. Clinical trial number: NCT00737568.
authors.affiliation: Department of Medicine, University of Toronto, Canada. Electronic address: scott.fung@uhn.ca.
authors.forename: Scott
authors.initials: S
authors.lastname: Fung
authors.affiliation: Department of Medicine, University of 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: Department of Adult Infectious Diseases, Medical University of Warsaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Horban
authors.affiliation: Clinic for Infectious and Tropical Diseases, Clinical Centre of Serbia, Serbia.
authors.forename: Mijomir
authors.initials: M
authors.lastname: Pelemis
authors.affiliation: Department of Medicine, Thomas Jefferson University, USA.
authors.forename: Hie-Won
authors.initials: HW
authors.lastname: Hann
authors.affiliation: Department of Internal Medicine, Uludag University, Turkey.
authors.forename: Selim
authors.initials: S
authors.lastname: Gurel
authors.affiliation: National Institute for Infectious Diseases, "Prof Dr Matei Bals", Romania.
authors.forename: Florin A
authors.initials: FA
authors.lastname: Caruntu
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: Benedetta
authors.initials: B
authors.lastname: Massetto
authors.affiliation: Gilead Sciences Inc, Foster City, CA, USA.
authors.forename: Kyungpil
authors.initials: K
authors.lastname: Kim
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: G Mani
authors.initials: GM
authors.lastname: Subramanian
authors.affiliation: Gilead Sciences Inc, Foster City, CA, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.affiliation: Gilead Sciences Inc, Foster City, CA, USA.
authors.forename: Leland J
authors.initials: LJ
authors.lastname: Yee
authors.affiliation: Toronto Liver Centre, Toronto, Canada.
authors.forename: Magdy
authors.initials: M
authors.lastname: Elkhashab
authors.affiliation: Clinic of Gastroenterology and Rheumatology, University Hospital Leipzig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.affiliation: University of Medicine and Pharmacy, Timisoara, Romania.
authors.forename: Ioan
authors.initials: I
authors.lastname: Sporea
authors.affiliation: Department of Gastroenterology, Ankara University, Turkey.
authors.forename: Cihan
authors.initials: C
authors.lastname: Yurdaydin
authors.affiliation: University Hospital Brno and Faculty of Medicine, Masaryk University Brno, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Husa
authors.affiliation: Department of Infectious and Liver Diseases, Medical University of Lodz, Poland.
authors.forename: Maciej S
authors.initials: MS
authors.lastname: Jablkowski
authors.affiliation: New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand.
authors.forename: Edward
authors.initials: E
authors.lastname: Gane
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D004279:DNA, Viral / Q000097:blood; D004311:Double-Blind Method; D016903:Drug Monitoring; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination / Q000379:methods; D000068679:Emtricitabine / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068698:Tenofovir / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D000068698:Tenofovir; D000068679:Emtricitabine
keywords: Bone mineral density; Emtricitabine; Lamivudine resistant; Renal function; Tenofovir disoproxil fumarate; Viral suppression