title: Early Viral Kinetics with Telbivudine, Tenofovir or Combination of Both in Immunotolerant Patients with Hepatitis B e Antigen-Positive Chronic Hepatitis B.
abstract: BACKGROUND
  Viral kinetics has proved useful in understanding antiviral potency, determining antiviral profiles and optimizing treatment strategy.
  
  
  METHODS
  This was a randomized, open-label study comparing the viral kinetics in 46 hepatitis B e antigen-positive patients during 12-week treatment with telbivudine monotherapy, tenofovir monotherapy or the combination of telbivudine plus tenofovir. A standard biphasic mathematical model was used to compare hepatitis B virus (HBV) DNA decay parameters.
  
  
  RESULTS
  Forty-six patients received telbivudine (n = 16), tenofovir (n = 14) or telbivudine plus tenofovir (n = 16). From baseline to Week 12, the mean (SD) reduction in HBV DNA levels was not significantly different between treatment groups: -3.9 (0.9) log10 copies/mL in telbivudine group, -4.2 (0.7) log10 copies/mL in tenofovir group, and -4.4 (1.0) log10 copies/mL in combination group. No significant difference was observed among the three groups for viral clearance rate per day (0.97, 1.02, and 0.88, respectively) or for infected cell loss rate per day (0.04, 0.05, and 0.05, respectively). Antiviral efficiency in blocking viral production was similar in the monotherapy groups (median; 99.7% in telbivudine group and 99.4% in tenofovir group), but was slightly better and more homogeneous in the combination treatment group than in the monotherapy groups: mean (SD), 99.1% (0.8%) and 98.8% (1.6%), respectively (Wald-Wolfowitz test; P = 0.038). All treatments were well tolerated and no serious adverse event was reported during the study. Of the 46 patients in the safety population, 23 experienced adverse events. Most of the adverse events were not suspected to be related to the study drug by the investigators.
  
  
  CONCLUSIONS
  Monotherapy with telbivudine or tenofovir showed similar antiviral effectiveness in HBV DNA reduction and viral kinetics of HBV DNA decay. Efficiency in blocking viral production was slightly improved in the combination treatment group compared to the monotherapy groups.
authors.affiliation: , 1501 Melbourne Plaza, 33 Queen's Road Central, Hong Kong S.A.R., China. dr_nancyleung@yahoo.com.hk.
authors.forename: Nancy W Y
authors.initials: NW
authors.lastname: Leung
authors.affiliation: Johann Wolfgang Goethe University Frankfurt Department of Medicine, Institute of Biostatistics and Mathematical Modeling, Theodor-Stern-Kai 7, Frankfurt am Main, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Herrmann
authors.affiliation: The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, China.
authors.forename: George K K
authors.initials: GK
authors.lastname: Lau
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong S.A.R., China.
authors.forename: Henry L Y
authors.initials: HL
authors.lastname: Chan
authors.affiliation: Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong S.A.R., China.
authors.forename: Tokutei M K
authors.initials: TM
authors.lastname: So
authors.affiliation: Klinikum der Johann Wolfgang Goethe-Universitaet, Frankfurt am Main, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Yu
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Aldo
authors.initials: A
authors.lastname: Trylesinski
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Nikolai V
authors.initials: NV
authors.lastname: Naoumov
keywords: Chronic hepatitis B; Combination therapy; Hepatitis B virus; Infectious diseases; Telbivudine; Tenofovir; Viral kinetics