title: Adefovir and lamivudine combination therapy in patients with entecavir-resistant chronic hepatitis B: antiviral responses and evolution of mutations.
abstract: OBJECTIVE
  This study was designed to prospectively evaluate the antiviral responses and evolution of resistance mutations during adefovir (ADV) plus lamivudine (LMV) therapy in patients with entecavir (ETV)-resistant hepatitis B virus (HBV) infection.
  
  
  METHODS
  Twenty chronic hepatitis B (CHB) patients who had been receiving ETV for more than 6 months and developed virologic breakthrough due to ETV resistance were consecutively enrolled.
  
  
  RESULTS
  Patients received ADV plus LMV therapy for 12 months. The baseline mean serum HBV DNA level was 5.59 ± 1.28 log10 IU/ml. The rtT184L/I/A/F (50%), rtS202G (25%) and mixed ETV-resistant mutations (25%) were detected at enrollment. The mean reduction in serum HBV DNA levels from baseline to 12 months was -2.3 ± 1.06 log10 IU/ml (p < 0.001). Seventeen patients were followed up for the full 12 months, and complete virologic response (HBV DNA <20 IU/ml) was observed in 4 patients (23.5%). Among the remaining 13 patients who still had detectable HBV DNA, 7 patients showed disappearance of ETV-resistant mutations or reduction of the proportion of ETV-resistant mutants. An ADV- and LMV-resistant mutant (rtA181T) emerged in 2 patients (11.7%).
  
  
  CONCLUSIONS
  ADV plus LMV combination therapy suppresses ETV-resistant mutants in the viral population and significantly reduces serum HBV DNA levels in ETV-resistant CHB patients.
authors.affiliation: Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea.
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Yim
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Suh
authors.forename: Yeon Seok
authors.initials: YS
authors.lastname: Seo
authors.forename: Chang Wook
authors.initials: CW
authors.lastname: Kim
authors.forename: Chang Don
authors.initials: CD
authors.lastname: Lee
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Myung Seok
authors.initials: MS
authors.lastname: Lee
authors.forename: Choong Kee
authors.initials: CK
authors.lastname: Park
authors.forename: Hee Bok
authors.initials: HB
authors.lastname: Chae
authors.forename: Moon Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Soon Koo
authors.initials: SK
authors.lastname: Baik
authors.forename: Yun Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Jung Il
authors.initials: JI
authors.lastname: Lee
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Lee
authors.forename: Sun Pyo
authors.initials: SP
authors.lastname: Hong
authors.forename: Soon Ho
authors.initials: SH
authors.lastname: Um
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006515:Hepatitis B virus / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000627:therapeutic use*; D011446:Prospective Studies; D044967:Serum / Q000821:virology; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine