Lamivudine compared with lamivudine and adefovir dipivoxil for the treatment of HBeAg-positive chronic hepatitis B☆
Received 29 July 2007; received in revised form 10 December 2007; accepted 11 December 2007. published online 28 February 2008.
Background/Aims
We aimed to evaluate nucleoside/nucleotide combination therapy in treatment-naïve HBeAg-positive patients with chronic hepatitis B (CHB).
Methods
One hundred and fifteen HBeAg-positive patients received lamivudine 100mg daily plus placebo (monotherapy) or lamivudine 100mg plus adefovir dipoxil 10mg daily (combination therapy) for 104 weeks in a randomized double-blind study.
Results
Time-weighted average change in serum HBV DNA from baseline up to week 16 was −4.20 log10copies/mL for both groups (p=0.936). At week 104, median serum HBV DNA change from baseline (log10copies/mL) for monotherapy and combination therapy was −3.41 versus −5.22, respectively. HBV DNA breakthrough was detected in 44% of monotherapy and 19% of combination therapy patients. The M204V/I mutation was detected in 43% (15/35) and 15% (6/41) of each group, respectively. ALT normalization at week 100 and 104 was 34% (19/56) in the monotherapy group and 45% (23/51) in the combination therapy group (p=0.018). By week 104, HBeAg seroconversion occurred in 20% of monotherapy and 13% of combination therapy patients. Both regimens were well tolerated.
Conclusions
Lower rates of resistance to lamivudine, lower serum HBV DNA levels and higher rates of ALT normalization were seen in the combination therapy group after two years. However, serological outcomes were similar.
☆ Clinical trial registration: NUC20912; GlaxoSmithKline Clinical Trial Register; http://ctr.gsk.co.uk. Dr. Brosgart is employee of Gilead Sciences, Foster City, CA. Drs. Woessner and Gardner are employees of GlaxoSmithKline Research and Development, Research Triangle Park, NC. Drs. Gray and Scott are employees of GlaxoSmithKline Research and Development, Greenford, Middlesex, UK. The other authors who have taken part in the research of this paper declared that they do not have a relationship with the manufacturers of the drug involved either in the past or present. They received funding from the manufacturers to carry out their research with the exception of Drs. Lai and Perrillo.
ABSTRACT