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


CONCLUSION
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.
['Yang|Song|S|', 'Xing|Huichun|H|', 'Wang|Qi|Q|', 'Wang|Xiaomei|X|', 'Liu|Shunai|S|', 'Cheng|Jun|J|']
D000225:Adenine D000328:Adult D000998:Antiviral Agents D004359:Drug Therapy, Combination D005260:Female D006147:Guanine D006515:Hepatitis B virus D019694:Hepatitis B, Chronic D006801:Humans D019259:Lamivudine D008297:Male D008875:Middle Aged D009154:Mutation D063065:Organophosphonates D012189:Retrospective Studies D014764:Viral Proteins
Adefovir dipivoxil Lamivudine Entecavir Multidrug resistance Hepatitis B virus