title: Emergence of adefovir-resistant mutants after reversion to YMDD wild-type in lamivudine-resistant patients receiving adefovir monotherapy.
abstract: BACKGROUND
  To evaluate the effect of reversion to YMDD wild-type on emergence of adefovir (ADV)-resistant mutation and antiviral activity of ADV in lamivudine (LAM)- resistant patients.
  
  
  METHODS
  We determined YMDD mutations and ADV-resistant mutations before and every 3 months during ADV monotherapy in 33 LAM-resistant patients using the restriction fragment mass polymorphism (RFMP) method.
  
  
  RESULTS
  Reversion to pure YMDD wild-type hepatitis B virus (HBV) occurred in 6% (2/33), 9% (3/33), 20% (4/20) and 35% (6/17) of patients after 12, 24, 36 and 48 weeks, respectively. Five (29%) patients were found to have pure YMDD mutants at 48 weeks of therapy. Among 33 patients, 4 (12%) patients developed ADV-resistant mutations at 48 weeks of therapy. Adefovir-resistant mutants emerged in all patients after reversion to YMDD wild-type HBV. The mean serum HBV reductions, evaluated at 24 weeks of therapy, were not different between patients with and without reversion to YMDD wild-type HBV (-3.1 log(10) copies/mL vs-3.4 log(10) copies/mL, P > 0.05).
  
  
  CONCLUSIONS
  ADV-resistant mutations emerged after reversion to YMDD wild-type in LAM-resistant patients who received ADV monotherapy. Thus, ADV add-on therapy may be necessary to reduce the incidence of developing ADV resistance in patients with LAM resistance.
authors.affiliation: Department of Gastroenterology, Genomic Research Center for Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Hyeok Choon
authors.initials: HC
authors.lastname: Kwon
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Cheong
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Cho
authors.forename: Jae Myoung
authors.initials: JM
authors.lastname: Choi
authors.forename: Sun Pyo
authors.initials: SP
authors.lastname: Hong
authors.forename: Soo-Ok
authors.initials: SO
authors.lastname: Kim
authors.forename: Wang Don
authors.initials: WD
authors.lastname: Yoo
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D005260:Female; D006509:Hepatitis B / Q000175:diagnosis / Q000188:drug therapy*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000627:therapeutic use*; D012150:Polymorphism, Restriction Fragment Length; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; C053001:adefovir; D000225:Adenine