Z Gastroenterol 2009; 47 - P151
DOI: 10.1055/s-0029-1241401

Tenofovir disoproxil fumarate (TDF) versus emtricitabine plus TDF (FTC/TDF) for treatment of chronic hepatitis B (CHB) in patients with persistent viral replication receiving adefovir dipivoxi

T Berg 1, B Möller 2, G Gerken 3, R Zachoval 4, U Spengler 5, H Hartmann 6, A Snow-Lampart 7, D Oldach 7, J Sorbel 7, K Borroto-Esoda 7, D Frederick 7, F Rousseau 7
  • 1Charité, Universitätsmedizin Berlin, Campus Virchow-Klinikum, Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Berlin, Germany
  • 2Internistische Gemeinschaftspraxis, Berlin, Germany
  • 3Universitätsklinik Essen, Essen, Germany
  • 4Klinikum der Universität München-Campus Großhadern, Med. Klinik und Poliklinik 2, München, Germany
  • 5Universitätsklinik Bonn, Medizinische Klinik und Poliklinik I, Bonn, Germany
  • 6Gastroenterologische Gemeinschaftspraxis Herne, Herne, Germany
  • 7Gilead Sciences Inc., Durham, United States

Introduction: This trial compared TDF monotherapy versus combination FTC/TDF therapy in CHB patients who had incomplete virologic response after receiving adefovir dipivoxil (ADV) for at least 6 months. In both blinded treatment arms, patients were permitted to change to open-label FTC/TDF after 24 weeks (W) if persistent viremia >400 copies/mL was confirmed.

Methodology: Entry criteria and baseline demographics/disease characteristics have been reported previously (Berg, et al., 2008 EASL). Among the 105 patients randomized and treated with TDF (N=53) or FTC/TDF (N=52) in this ongoing study, 57% had prior lamivudine (LAM) experience. Di-deoxy sequencing at baseline confirmed 13 with LAM-associated mutations (LAM-r) and 10 with ADV-associated mutations (ADV-r). An intention-to-treat analysis was conducted using both non-completers=failures (NC=F) and non-completers/switches=failures (NC/S=F). W72 data are available and W96 will be presented.

Results: Sixteen and 9 patients in the TDF and FTC/TDF arms, respectively, switched to open-label FTC/TDF after W24; 8 discontinued (2 in TDF arm, 6 in FTC/TDF arm), none due to adverse events (AEs). Through W72 using NC=F analysis, 87% and 85% of patients originally randomized to TDF and FTC/TDF, respectively, had HBV DNA <400 copies/mL; notably, 11/13 with LAM-r and 9/10 with ADV-r were <400 copies/mL. Considering NC/S=F at W72, 65% and 77% (TDF and FTC/TDF arms) were still on initial randomized therapy with HBV DNA <400 c/mL (p=0.223), which was consistent with the W48 response in both arms. ALT was normal in 81% (TDF) and 75% (FTC/TDF) of patients. No unexpected AEs, or AEs related to renal function, bone events or fractures related to study drug, or clinically important changes in renal laboratory parameters were noted.

Conclusions: The majority of patients on either blinded treatment or open-label FTC/TDF had HBV DNA <400 copies/mL at Week 72. When NC/S=F was considered, a greater proportion of patients randomized to FTC/TDF achieved this endpoint (although this difference was not statistically significant). Both TDF and FTC/TDF were well-tolerated. Thus, the strategy of initial monotherapy was effective in most patients and did not appear to attenuate subsequent response when combination therapy was initiated.