title: Viral kinetics in patients with lamivudine-resistant hepatitis B during adefovir-lamivudine combination therapy.
abstract: OBJECTIVE
  Mathematical analysis of viral kinetics during lamivudine-adefovir combination therapy has not yet been performed in patients with lamivudine-resistant hepatitis B.
  
  
  METHODS
  In 8 patients with lamivudine-resistant hepatitis B, adefovir dipivoxil (10 mg/day) was added to ongoing lamivudine. Viral decay during the first 8 weeks of combination therapy was described by a biphasic model to determine the efficacy: epsilon, of blocking viral production, the clearance: c, of free virus, and the loss of infected cells: delta.
  
  
  RESULTS
  Median epsilon was 98%, median c was 0.7/day, and median delta was 0.07/day. No significant association was found between viral kinetic and baseline parameters and virologic and biochemical treatment response. When compared with viral kinetic constants reported for higher dose adefovir dipivoxil monotherapy, epsilon was lower (P=0.026) and delta was higher (P=0.008) in this study whereas c did not differ between both studies.
  
  
  CONCLUSIONS
  Although a recent study did not show any differences in the reduction of HBV DNA comparing monotherapy with adefovir dipivoxil to adefovir-lamivudine combination therapy in patients with lamivudine-resistant chronic hepatitis B, mathematical analysis of early viral kinetics suggests an additional effect of lamivudine on the infected cell loss during adefovir-lamivudine combination therapy.
authors.affiliation: Klinik für Innere Medizin II, Universitätsklinikum des Saarlandes, Kirrberger Str., 66421 Homburg/Saar, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Mihm
authors.forename: Barbara Christine
authors.initials: BC
authors.lastname: Gärtner
authors.forename: Dominik
authors.initials: D
authors.lastname: Faust
authors.forename: Wolf Peter
authors.initials: WP
authors.lastname: Hofmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Eva
authors.initials: E
authors.lastname: Herrmann
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood / Q000187:drug effects / Q000235:genetics; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D009154:Mutation / Q000187:drug effects; D063065:Organophosphonates / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; C053001:adefovir; D000225:Adenine