title: Overlap/switch to adefovir monotherapy for lamivudine-resistant patients who responded to combination therapy: a pilot controlled study.
abstract: OBJECTIVE
  The aim of this study was to investigate the outcome of overlap/switch to adefovir dipivoxil (ADV) monotherapy for chronic hepatitis B (CHB) patients with lamivudine (LAM)-resistant HBV, who responded to LAM plus ADV combination therapy.
  
  
  METHODS
  In 29 of 35 LAM-resistant CHB patients, serum HBV-DNA levels decreased to <3.7 log genome equivalent (LGE)/mL at 12 months after LAM plus ADV combination therapy, defined as complete virological response (CVR). The 29 CVR patients were randomly allocated to continuation of combination therapy or switch to ADV monotherapy within 12 months. The cumulative rates of sustained CVR were compared between the two groups.
  
  
  RESULTS
  The follow-up duration after randomization was 19.3-36.7 months (median, 28.2 months) for the combination group and 21.0-36.4 months (29.0 months) for the overlap/switch group. The cumulative rate of sustained CVR during the follow-up period was 100% in all patients of both groups. The total medical expenses during follow-up after randomization were median US$20,949 for the combination group and US$16,107 for the overlap/switch group (p=0.012). Overlap/switch to ADV monotherapy sufficiently repressed the replication of LAM-resistant mutants without the development of ADV-resistant mutants. The rate of sustained CVR was not influenced by treatment regimen (continuation of combination therapy or switching to ADV monotherapy), the duration of the overlap period, or patient and virological characteristics.
  
  
  CONCLUSIONS
  In LAM-resistant CHB patients who achieved CVR to LAM plus ADV combination therapy, CVR was maintained after overlap/switch to ADV monotherapy, suggesting that it could be a useful regimen for such patients.
authors.affiliation: Department of Gastroenterology and Hepatology, Kashiwa Hospital, Kashiwa, Japan. mashu0914@hotmail.co.jp
authors.forename: Mashu
authors.initials: M
authors.lastname: Aizawa
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsubota
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Fujise
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Sato
authors.forename: Masashi
authors.initials: M
authors.lastname: Baba
authors.forename: Masashi
authors.initials: M
authors.lastname: Takamatsu
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Namiki
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ohkusa
authors.forename: Hisao
authors.initials: H
authors.lastname: Tajiri
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D000368:Aged; D024882:Drug Resistance, Viral / Q000187:drug effects* / Q000502:physiology; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage*; D010865:Pilot Projects
chemical_list: D063065:Organophosphonates; D019259:Lamivudine; C053001:adefovir; D000225:Adenine