De novo entecavir+adefovir dipivoxil+lamivudine triple-resistance mutations resulting from sequential therapy with adefovir dipivoxil, and lamivudine

Annals of Clinical Microbiology and Antimicrobials

Short Report

Huichun Xing¹  Xiaomei Wang¹  Qi Wang¹  Song Yang¹  Jun Cheng²  Shunai Liu³ 

[1] Center of Hepatology, Beijing Ditan Hospital, Capital Medical University, 8 East Jingshun Street, Chaoyang District, 100015, Beijing, China;Center of Hepatology, Beijing Ditan Hospital, Capital Medical University, 8 East Jingshun Street, Chaoyang District, 100015, Beijing, China;Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, 8 East Jingshun Street, Chaoyang District, 100015, Beijing, China;Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, 8 East Jingshun Street, Chaoyang District, 100015, Beijing, China;

关键词: Hepatitis B virus;    Multidrug resistance;    Entecavir;    Adefovir dipivoxil;    Lamivudine;   

DOI  :  10.1186/s12941-016-0138-0

 received in 2015-11-05, accepted in 2016-03-29,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundEntecavir-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.ResultsWe 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.ConclusionDe 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.

【 授权许可】

CC BY   
© Yang et al. 2016