Tenofovir disoproxil fumarate (TDF) for the treatment of HBeAg-positive chronic Hepatitis B: Week 72 TDF data and week 24 Adefovir dipivoxil switch data (Study 103)

Aims: TDF, a nucleotide analogue and obligate chain terminator, has potent activity against hepatitis B virus (HBV).

Methods: Subjects with HBeAg positive (+) chronic hepatitis B (CHB) were randomized 2:1 to double-blind TDF (N=176) or ADV (N=90) for the first 48 weeks. After 48 weeks eligible subjects with week (WK) 48 biopsy were switched to TDF for up to an additional 4 years. HBV DNA was measured using the Roche COBAS TaqMan assay.

Results: Eighty-four subjects originally randomized to ADV initiated TDF at WK48. Seventy-two subjects had HBV DNA >400 c/ml just prior to switching to TDF. At WK72 after 24 weeks of TDF, 66/84 subjects had HBV DNA <400 copies/mL; 54 of the 72 viremic subjects and 12/12 subjects with HBV DNA <400 c/mL at WK48. For subjects treated with TDF during the first 48 weeks, 154 subjects continued TDF and 22 did not (16/22 were <400at their last visit): 11 discontinued (DC) prior to WK48 and 11 did not enter the study extension (7 refused WK48 biopsy, 2 withdrew consent, 1 lost to follow-up, 1 subject at a site that didn't participate in the extension). At WK72, 129 subjects had HBV DNA <400 c/mL, 16 had HBV DNA >400 c/mL and 9 were missing data at WK72 (6 of whom had HBV DNA <400 c/mL at their last visit). For the limited HBeAg and HBsAg data through WK64, overall 51/216 subjects experienced HBeAg seroconversion and 7 subjects (all from the group randomized to TDF in the first 48 weeks) lost HBsAg. TDF was well tolerated through WK72.

Conclusion: Continuous therapy with TDF past 48 weeks produced additional viral suppression, HBeAg seroconversion and HBsAg loss. A switch to TDF after 48 weeks of ADV produced significant additional viral suppression. Tolerability of TDF for 72 weeks was good.