Entecavir plus tenofovir combination therapy for chronic hepatitis B in patients with previous nucleos(t)ide treatment failure

摘要

Background and aimsIn patients with chronic hepatitis B (CHB) who have failed on other nucleos(t)ide analogs (NUCs), the combination of entecavir (ETV) plus tenofovir disoproxil fumarate (TDF), two potent agents with non-overlapping resistance profiles, may provide a single rescue regimen.MethodsIn this single-arm, open-label study, 92 CHB patients with a primary non-response, partial response, or virologic breakthrough on their current NUC were switched to ETV (1?mg) plus TDF (300?mg) and treated for 96?weeks.ResultsAt baseline, 62?% of patients were HBeAg(+) and mean HBV DNA was 4.4?log10IU/mL. Patients had received ≥1 line of prior NUC therapy, with the latest regimen consisting of monotherapy with ETV (53?%), lamivudine (LVD 22?%), TDF (12?%), adefovir (ADV 4?%), or telbivudine (2?%), or combinations of these agents (7?%); 58?% had evidence of single- or multidrug resistance mutations (LVD 52?%, ETV 26?%; ADV 7?%). Response rates for HBV DNA <50?IU/mL were 76?% (70/92) at week 48 (primary endpoint), and 85?% (78/92) at week 96, including 80?% (16/20) in prior LVD failures, 100?% (4/4) in ADV failures, 82?% (9/11) in TDF failures, and 88?% (42/48) in ETV failures. No treatment-emergent resistance to ETV or ADV was observed. ETV/TDF was well tolerated, with no significant renal or additive toxicities observed.ConclusionsIn NUC-experienced patients who have failed prior NUC therapy, ETV/TDF was well tolerated and effective, achieving virologic suppression through 96?weeks in the majority (85?%), irrespective of prior NUC exposure, without occurrence of treatment-emergent resistance to either agent.