title: De novo entecavir+adefovir dipivoxil+lamivudine triple-resistance mutations resulting from sequential therapy with adefovir dipivoxil, and lamivudine.
abstract: BACKGROUND
  Entecavir-resistance mutations are commonly induced by entecavir treatment in chronic hepatitis B patients. However, entecavir+adefovir dipivoxil+lamivudine triple-resistance mutations induced by sequential or combination treatment with lamivudine and adefovir dipivoxil have never been reported.
  
  
  RESULTS
  We retrospectively reviewed 1200 patients who had been tested for anti-HBV drug resistance at Beijing Ditan Hospital of Capital Medical University, and five patients showing multidrug resistance to lamivudine and adefovir dipivoxil were enrolled. Stored serum samples were used for genetic analysis, which yielded a total of 135 clones. Entecavir+adefovir dipivoxil+lamivudine triple-resistance mutations were identified in 60 % (3/5) entecavir-naïve patients who received sequential therapy with adefovir dipivoxil and lamivudine. Specifically, we found one rtM204I+rtL180 M+rtM250 V+rtA181 V clone among 23 clones from patient 1 (4.35 %), one rtM204 V+vrtL180 M +rtM250 V+rtA181 V clone among 24 clones from patient 2 (4.17 %), and 2 clones harboring rtM204 V+rtL180 M+rtM250 V+rtA181 V and rtM204 V+rtL180 M+rtI169 V+rtA181 V among 20 clones from patient 3 (10.0 %). The other 2 patients showed multidrug resistance after lamivudine/telbivudine and adefovir dipivoxil combination therapy, but no entecavir-resistance mutations were found in these two patients.
  
  
  CONCLUSIONS
  De novo entecavir+adefovir dipivoxil+lamivudine triple-resistance mutations can be induced by sequential therapy with adefovir dipivoxil and lamivudine in patients who never take entecavir. These results provide important information for sequential therapy with adefovir dipivoxil and lamivudine and the use of entecavir as a rescue therapy for these patients with multidrug resistance.
authors.affiliation: Center of Hepatology, Beijing Ditan Hospital, Capital Medical University, 8 East Jingshun Street, Chaoyang District, Beijing, 100015, China.
authors.forename: Song
authors.initials: S
authors.lastname: Yang
authors.affiliation: Center of Hepatology, Beijing Ditan Hospital, Capital Medical University, 8 East Jingshun Street, Chaoyang District, Beijing, 100015, China.
authors.forename: Huichun
authors.initials: H
authors.lastname: Xing
authors.affiliation: Center of Hepatology, Beijing Ditan Hospital, Capital Medical University, 8 East Jingshun Street, Chaoyang District, Beijing, 100015, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Center of Hepatology, Beijing Ditan Hospital, Capital Medical University, 8 East Jingshun Street, Chaoyang District, Beijing, 100015, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, 8 East Jingshun Street, Chaoyang District, Beijing, 100015, China.
authors.forename: Shunai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Center of Hepatology, Beijing Ditan Hospital, Capital Medical University, 8 East Jingshun Street, Chaoyang District, Beijing, 100015, China. chengj0817@sina.cn.|Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, 8 East Jingshun Street, Chaoyang District, Beijing, 100015, China. chengj0817@sina.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects*; D063065:Organophosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D014764:Viral Proteins; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; D000225:Adenine; C106812:adefovir dipivoxil
keywords: Adefovir dipivoxil; Entecavir; Hepatitis B virus; Lamivudine; Multidrug resistance