RANDOMIZED TRIAL OF TENOFOVIR MONOTHERAPY VERSUS TENOFOVIR PLUS ENTECAVIR COMBINATION THERAPY IN CHRONIC HEPATITIS B PATIENTS WITH GENOTYPIC RESISTANCE MUTATIONS TO ADEFOVIR

초록

Background and Aims: Antiviral efficacy of tenofovir monotherapy in patients who harbor adefovir-resistant hepatitis B virus (HBV) is controversial. Methods: In this multi-center open-label trial, patients who had HBV with genotypic resistance mutations to adefovir and serum HBV DNA concentration >60 IU/mL were randomized to tenofovir disoproxil fumarate (TDF, 300 mg/day) monotherapy (n = 50) or to TDF (300 mg/day) plus entecavir (ETV, 1 mg/day) combination therapy (n = 52), and were included in the intention-to-treat analyses. Results: At baseline, patients’ mean serum HBV DNA was 3.9 log10 IU/mL (SD 1.6). All 102 patients had documented adefovir-resistance mutations; 66 rtA181V/T, 6 rtN236T, and 30 rtA181V/T+rtN236T. Fifty-one patients also harbored lamivudine-resistance mutations, and 35 had resistance mutations to all of adefovir, lamivudine and entecavir. Two patients in TDF+ETV group withdrew at 4 weeks and 12 weeks, respectively. One-hundred patients completed 36 weeks of treatment. The number of patients with serum HBV DNA <15 IU/mL was similar between TDF group (n = 30, 60%) and TDF+ETV group (n = 30, 58%) at week 36 (P = 0.81). The mean reduction in HBV DNA levels from baseline was also similar between the two groups (−2.9 log10 IU/mL vs. −3.2 log10 IU/mL; P = 0.42). Virological breakthrough was observed in a patient in TDF group at 36 weeks of treatment, which was attributed to documented low adherence and resolved afterward. Safety and adverse event profiles were similar in the two groups. Conclusions: TDF monotherapy provides similar virological response compared with TDF+ETV combination therapy during 36 weeks of treatment in patients who have adefovir-resistant HBV. No patient developed virological breakthrough associated with TDF-resistance.