title: Impact of early viral kinetics on T-cell reactivity during antiviral therapy in chronic hepatitis B.
abstract: BACKGROUND
  The patterns of hepatitis B viral dynamics during different antiviral therapies and the associated changes in HBV-specific T-cell reactivity are not well defined.
  
  
  METHODS
  We investigated the impact of early viral load decline on virus-specific T-cell reactivity in 30 hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B randomized to monotherapy with adefovir dipivoxil (ADV) or in combination with emtricitabine (ADV/FTC). Viral kinetics were analysed by mathematical modelling. T-cell reactivity to HBV core and/or surface antigens and natural killer T cell frequency were tested longitudinally, baseline to week 48, using EliSPOT assays and/or flow cytometry.
  
  
  RESULTS
  Mathematical modelling of early HBV kinetics identified two subsets of patients: 11 fast responders (undetectable viraemia by week 12; eight on ADV/FTC three on ADV) and 19 slow responders who remained viremic (six on ADV/FTC 13 on ADV). The rate of infected hepatocyte loss was higher in fast than in slow responders (P = 0.0007), and correlated inversely with pre-treatment levels of intrahepatic covalently closed circular HBV DNA. The frequency of HBV core-specific CD4+ T-cells increased significantly only in fast responders, peaking between week 16 and 24, while the HBV surface-specific CD4+ T-cells increased in both subsets. These changes in CD4+ T-cell reactivity were transient however, and no increase in HBV-specific CD8+ T-cells was observed. By week 48, HBeAg seroconversion occurred only in 3/30 (10%) patients.
  
  
  CONCLUSIONS
  Early viraemia clearance facilitates recovery of virus-specific CD4+ T-cell reactivity, but appears insufficient to establish clinically relevant antiviral immunity.
authors: Department of Medicine, Queen Mary Hospital, Hong Kong SAR, China. gkkla@netvigator.com
authors: George K K
authors: GK
authors: Lau
authors: Helen
authors: H
authors: Cooksley
authors: Ruy M
authors: RM
authors: Ribeiro
authors: Kimberly A
authors: KA
authors: Powers
authors: Emi
authors: E
authors: Shudo
authors: Scott
authors: S
authors: Bowden
authors: Chee-Kin
authors: CK
authors: Hui
authors: Jane
authors: J
authors: Anderson
authors: Jeff
authors: J
authors: Sorbel
authors: Elsa
authors: E
authors: Mondou
authors: Franck
authors: F
authors: Rousseau
authors: Sharon
authors: S
authors: Lewin
authors: Alan S
authors: AS
authors: Perelson
authors: Stephen
authors: S
authors: Locornini
authors: Nikolai V
authors: NV
authors: Naoumov
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004279:DNA, Viral / Q000096:biosynthesis / Q000187:drug effects*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood; D006511:Hepatitis B Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D022781:Hepatocytes / Q000187:drug effects / Q000821:virology; D006801:Humans; D007111:Immunity, Cellular; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D018448:Models, Immunological; D063065:Organophosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000821:virology; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000821:virology; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006511:Hepatitis B Antigens; D063065:Organophosphonates; D003841:Deoxycytidine; D000068679:Emtricitabine; D000225:Adenine; C106812:adefovir dipivoxil