Department of Internal Medicine, Pusan National University School of Medicine, Busan, Republic of Korea.
Growing numbers of chronic hepatitis B (CHB) patients in the Asia Pacific region have failed first-line therapy with low genetic barrier drugs. This prospective, 96 week study investigated the antiviral efficacy, safety and tolerability of switching to entecavir versus maintaining lamivudine in CHB patients with a partial virologic response to lamivudine.
A total of 72 HBeAg-positive patients, with serum HBV DNA ≥60 IU/mL after at least 6 months lamivudine monotherapy were randomized 1:1 to receive either entecavir 1.0 mg/day, or continued lamivudine 100 mg/day.
Mean duration of prior lamivudine treatment was 15.1 months in the lamivudine-maintained, and 16.1 months in the entecavir-switch patients, with mean baseline HBV DNA levels of 4.66 and 4.55 log(10) IU/mL for lamivudine-maintained and entecavir-switch patients, respectively. A greater proportion of entecavir-switch than lamivudine-maintained patients achieved undetectable HBV DNA at all time-points (67.6% versus 11.4% at Week 96 [P<0.001]). Entecavir-switch patients achieved a greater mean decrease in HBV DNA level by Week 4, maintained through Week 96. Entecavir-switch patients with baseline HBV DNA <5 log(10) IU/mL were more likely to achieve a virologic response at Week 96. Six entecavir-switch (17.6%) and two lamivudine-maintained (5.7%) patients achieved HBeAg loss, and three entecavir (8.8%) and one lamivudine (2.9%) patients achieved HBeAg seroconversion. Genotypic resistance to assigned intervention emerged in 82.9% (29/35) of lamivudine-maintained patients, and in 3% (1/34) of entecavir-switch patients after 96 weeks.
Switching to entecavir in patients with a partial virologic response to lamivudine resulted in increased virologic efficacy and lower rates of antiviral resistance than maintaining lamivudine.