Combination adefovir-lamivudine prevents emergence of adefovir resistance in lamivudine-resistant hepatitis B.
OBJECTIVE
The outcomes of lamivudine-resistant chronic hepatitis B patients treated with long-term adefovir dipivoxil have not been well described. This study aims to characterize the virological and biochemical response and to determine factors that may influence the development of resistance to adefovir.


METHODS
A retrospective review was conducted on all patients with lamivudine-resistant chronic hepatitis B treated with adefovir for a minimum of 6 months at two tertiary referral centers.


RESULTS
Data on 161 patients were analyzed. Seventy-two percent achieved an initial virological response with eventual normalization of alanine aminotransferase in only 67% of patients. Seventeen patients developed adefovir resistance with cumulative resistance rates of 3.2%, 8.8%, and 18% at 12, 24, and 36 months, respectively. Twelve (71%) of these patients had a biochemical breakthrough, with one death from fulminant hepatic failure. The median duration of lamivudine crossover was 1 month in adefovir-resistant patients, compared with 12 months for the remainder of the cohort (P < 0.01). Longer crossover therapy reduced the adefovir resistance rate, but did not eliminate it. No adefovir resistance is reported in those who were continued on long-term combination lamivudine-adefovir without a period of adefovir monotherapy.


CONCLUSIONS
Combination lamivudine-adefovir therapy protected against the emergence of adefovir resistance.
van der Poorten
David
D
Department of Gastroenterology and Hepatology, Concord Hospital, Sydney, New South Wales, Australia.
Prakoso
Emilia
E
Khoo
Teh-Liane
TL
Ngu
Meng C
MC
McCaughan
Geoffrey W
GW
Strasser
Simone I
SI
Lee
Alice U
AU
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004351:Drug Resistance; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006513:Hepatitis B e Antigens / Q000032:analysis; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D012189:Retrospective Studies
D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D019259:Lamivudine; C053001:adefovir; D000225:Adenine