title: Lamivudine plus adefovir or entecavir for patients with chronic hepatitis B resistant to lamivudine and adefovir.
abstract: OBJECTIVE
  Little is known about the optimal management of patients with chronic hepatitis B (CHB) who developed multiple-drug resistance.
  
  
  METHODS
  We assessed 91 patients with compensated CHB who developed adefovir-resistant mutations during adefovir monotherapy for lamivudine-resistant CHB. Of these, 41 were treated with a combination of lamivudine plus adefovir (LAM+ADV group) and 50 were treated with entecavir monotherapy (ETV group).
  
  
  RESULTS
  There were no significant differences between the two groups in baseline characteristics, including serum HBV DNA levels (p>0.05). The rate of virologic non-response (HBV DNA reduction <1 log(10) IU/ml at 6 months) was significantly greater in the LAM+ADV than in the ETV group (51.2% vs. 16.0%, p<0.01). At 12 months, HBV DNA declined less in the LAM+ADV than in the ETV group (-1.49+/-1.78 vs. -3.47+/-2.13 log(10) IU/ml, p<0.01). Only 12.2% and 22.0% of patients in the LAM+ADV and ETV groups, respectively, achieved complete virologic response (HBV DNA <60 IU/ml) at 12 months. Multivariable analysis showed that LAM+ADV group (OR=0.08, CI=0.02-0.28) and the presence of the rtA181V/T mutation (OR=0.21, CI=0.05-0.91) were independently associated with a decreased rate of virologic response (HBV DNA <2000 IU/ml) at 12 months.
  
  
  CONCLUSIONS
  In patients with CHB resistant to lamivudine and adefovir, combination therapy with these two drugs was not effective and was inferior to entecavir monotherapy in suppressing HBV DNA. However, the response to entecavir monotherapy was also not optimal. These results emphasize the importance of preventing the development of multidrug-resistant HBV and of exploration for adequate combination therapy in treatment of multidrug-resistant CHB.
authors.affiliation: Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Nae-Yun
authors.initials: NY
authors.lastname: Heo
authors.forename: Young-Suk
authors.initials: YS
authors.lastname: Lim
authors.forename: Han Chu
authors.initials: HC
authors.lastname: Lee
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Chung
authors.forename: Yung Sang
authors.initials: YS
authors.lastname: Lee
authors.forename: Dong Jin
authors.initials: DJ
authors.lastname: Suh
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005814:Genes, Viral; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000008:administration & dosage*; D019562:Viral Load / Q000187:drug effects / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine