Early viral kinetics of telbivudine and entecavir: results of a 12-week randomized exploratory study with patients with HBeAg-positive chronic hepatitis B

Abstract

We characterized the early viral kinetic profiles of telbivudine and entecavir and the effects of these potent nucleoside analogs on hepatitis B virus (HBV) DNA and alanine aminotransferase levels in adults with hepatitis B e antigen-positive compensated chronic hepatitis B. Forty-four patients were enrolled in this open-label, parallel-group, multicenter study and randomized to receive telbivudine or entecavir for 12 weeks. Reductions in hepatitis B virus DNA and alanine aminotransferase levels from baseline to weeks 2, 4, 8, and 12 were assessed. Viral kinetic parameters, including viral clearance per day, loss of infected cells per day, and efficiency of inhibition of viral production, were estimated by using a biphasic mathematical model. Statistical analyses were limited to descriptive analyses. The 2 treatment groups achieved similar reductions in HBV DNA and alanine aminotransferase levels. Mean reductions in levels of hepatitis B virus DNA at week 12 were 6.6 +/- 1.6 and 6.5 +/- 1.5 log(10) copies/ml for the telbivudine- and entecavir-treated patients, respectively. There were no significant differences between groups in values for mean viral clearance per day, mean loss of infected cells per day, or efficiency of blocking viral production. The safety profiles for both medications were favorable. During the first 12 weeks of treatment, telbivudine and entecavir demonstrated similar antiviral potencies, resulting in a rapid and profound suppression of serum hepatitis B virus DNA and reduction of alanine aminotransferase levels. No differences in the effects of these 2 agents on early viral kinetics were observed. Both medications were well tolerated.

FIG. 1.

Effects of telbivudine and entecavir on early serum HBV and ALT kinetics. (A) Mean (± standard deviation [SD]) change from baseline in log₁₀ HBV DNA levels with telbivudine and entecavir. (B) Mean (±SD) ALT levels over time with telbivudine and entecavir.

FIG. 2.

Change from baseline in log₁₀-transformed HBV DNA over time by patients (ITT population).

FIG. 3.

Box plots for the efficiency of blocking virus protection by treatment group (ITT population). The boxes show the ranges between the 25% and 75% quintiles (the middle half of the estimated parameters). The median is shown by the line, and the mean is indicated by the cross. The vertical lines represent the range (the smallest and largest values in each case).