Background and aims: TDF and FTC are nucleotide/side analogues, obligatory chain terminators, with potent activity against hepatitis B virus (HBV). The primary objective of this Phase 2 study was to characterize the antiviral activity of TDF 300mg QD versus the fixed-dose combination of TDF 300mg plus FTC 200mg QD in CHB subjects with incomplete virologic response while receiving ADV 10mg QD for at least 6 months.
Methods: This is an ongoing, randomized, double-blind, double-dummy multinational study of monoinfected subjects with CHB randomized in a 1:1 ratio to receive TDF or TDF+FTC. Entry criteria included 18–69 years old, compensated liver disease, current treatment with ADV [and TDF naive], plasma HBV DNA levels >1000 copies/mL, ALT <10x the upper limit of normal (ULN), no evidence of hepatocellular carcinoma. HBV DNA was measured using the Roche COBAS TaqMan HBV assay. Sequence analysis was performed by di-deoxy sequencing.
Results: 105 subjects were randomized and treated with a TDF-containing regimen, the 24-week pooled, treatment-blind data are described. Subjects were of mean age 39 years, 76% male, 42% Caucasian, 42% Asian and 57% lamivudine-experienced. Among subjects with available resistance data, approximately 11% harbored ADV-associated mutations at baseline. At baseline, mean HBV DNA was 5.97 log10 copies/mL, 51% had ALT >ULN, 73% were HBeAg+ and mean prior ADV exposure was 423 days (140–917). Through 24 weeks, 68% achieved HBV DNA <400 copies/mL (65% of HBeAg+ subjects and 79% of HBeAg-). Normal ALT was achieved in 66% of subjects. The TDF-containing regimens have been well-tolerated. Resistance surveillance is ongoing, and safety and efficacy data for all 105 subjects through 48 weeks will be presented.
Conclusions: By Week 24, the majority of subjects who were viremic on ADV experienced robust virologic suppression after switching to a TDF-containing regimen. These results are consistent with that observed in antiviral activity of TDF in studies of treatment-naïve subjects treated with TDF alone. The TDF-containing regimens' safety and tolerability profiles in this HBV heavily pretreated population were favorable and consistent with the known safety profile in HIV-infected subjects.
