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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
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.