One hundred and two
LAM-resistant patients and 79 without
LAM resistance (36 naïve and 43 prior
LAM exposure) treated with
adefovir for >12 months were prospectively examined.
RESULTS: Cumulative incidences of
adefovir resistance at month 12, 24, 36 and 48 were 3.9, 21.1, 31.8 and 43% respectively in
LAM-resistant patients.
Cirrhosis was a significant risk factor for
adefovir resistance. A similar rate of
adefovir resistance was observed for
LAM-resistant patients and those with prior
LAM exposure without resistance. Regarding
LAM-resistant patients, compared with those having hepatitis B virus (HBV)
DNA levels <300 copies/ml, patients having HBV
DNA levels >10(4) copies/ml at week 24 of
therapy had a hazard ratio (HR) of 9.8 for
adefovir resistance development, while those without
LAM resistance having the same HBV
DNA levels at week 48 had a similar HR (9.5). Multidrug-resistant (LAM+adefovir) variants were detected by direct sequencing in three of 35
LAM-resistant patients treated with a switch to
adefovir. Two of them had resistant mutations to both drugs on the same viral genome as determined by molecular cloning and sequencing.
CONCLUSION: The incidence of
adefovir resistance was high in
LAM-resistant patients treated with sequential
adefovir. High HBV
DNA levels at week 24 and 48 of
therapy were the strongest predictors for
adefovir resistance development in patients with and without
LAM resistance respectively.