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DOI: 10.1055/s-0029-1241526
Safety and efficacy in lamivudine experienced chronic hepatitis B (CHB) patients treated for two years with tenofovir disoproxil fumarate
Introduction: Tenofovir disoproxil fumarate (TDF) is active against lamivudine resistant hepatitis B virus (HBV). Response to TDF treatment in a subset of patients from the phase 3, studies 102 (HBeAg-negative patients) and 103 (HBeAg-positive patients) previously treated for >12 weeks with lamivudine or emtricitabine (LAM-experienced) was compared to LAM-naïve patients in these two studies.
Goal: To determine if the safety and efficacy of TDF treatment is comparable at week (W) 96 in LAM-experienced and LAM-naïve patients.
Methods: In studies 102 and 103, CHB patients were randomized 2:1 to double-blind, once daily TDF 300mg or adefovir dipivoxil (ADV) 10mg. At W48, patients with a W48 biopsy initiated open-label TDF for up to 7 additional years. A total of 426 patients were initially randomized to TDF (51 LAM-experienced and 375 LAM-naïve). The majority of LAM-experienced patients were HBeAg-negative (N=41).
Results: Forty-seven LAM-experienced patients and 350 LAM-naïve patients completed 96 weeks (2 years) of TDF treatment. Baseline demographics and disease characteristics of LAM-experienced patients included a mean age of 45 years, 78% Caucasian, 71% male and mean HBV DNA of 7.2 log10copies/mL. A similar proportion of patients achieved viral suppression (HBV DNA <400 c/mL; 69 IU/mL) at week 96 in the LAM-experienced versus LAM-naïve subgroup: 92% versus 84% (ITT) and 98% versus 95% (on-treatment). Mean ALT at W96 in LAM-experienced and LAM-naïve patients was 31.7 U/L and 35.5 U/L, respectively. No LAM-experienced patient achieved HBsAg loss. No HBV pol/RT amino acid substitutions associated with TDF resistance were detected through 96 weeks of TDF monotherapy in LAM-experienced patients. Cumulatively over 2 years, 2 LAM-experienced patients had serious AEs considered related to TDF (ALT flares) and no LAM-experienced patient discontinued due to an AE. No LAM-experienced patient had a confirmed decrease in creatinine clearance <50 mL/min or confirmed increase in creatinine of ≥0.5mg/dL.
Conclusion: The safety, efficacy and resistance surveillance results for 96 weeks of TDF treatment were similar in LAM-experienced and LAM-naïve CHB patients. Longer follow up is ongoing.