Lamivudine plus adefovir or entecavir for patients with chronic hepatitis B resistant to lamivudine and adefovir.
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.
Heo
Nae-Yun
NY
Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Lim
Young-Suk
YS
Lee
Han Chu
HC
Chung
Young-Hwa
YH
Lee
Yung Sang
YS
Suh
Dong Jin
DJ
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
D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine