Background/Aims: Suboptimal responses to lamivudine or telbivudine plus adefovir (LAM/LdT+ADV) rescue therapy are common in patients with LAM-resistant hepatitis B virus (HBV) infections. We compared patients switched to entecavir plus tenofovir (ETV+TDF) to those maintained on LAM/LdT+ADV. Methods: This prospective randomized controlled trial examined 91 patients whose serum HBV DNA levels were greater than 60 IU/mL after at least 24 weeks of treatment with LAM/LdT+ADV for LAM-resistant HBV. Patients were randomized to receive a new treatment (ETV+TDF, n=45) or maintained on the same treatment (LAM/LdT+ADV, n=46) for 48 weeks. Patients with baseline ADV resistance were excluded. Results: Compared to LAM/LdT+ADV group, ETV+TDF group had more patients with a virologic response (42/45 [93.33%] vs. 3/46 [6.52%], P<0.001) and had a greater mean reduction in serum HBV DNA level from baseline (-4.16 vs.-0.37 log10 IU/mL, P<0.001). Multivariate analysis indicated that high baseline HBV DNA level (P=0.005) and LAM/LdT+ADV maintenance therapy (P=0.001) were negatively associated with virologic response. At week 48, additional ADV-or ETVassociated mutations were cleared in ETV+TDF group, but such mutations were present in 4.3% of patients in LAM/ LdT+ADV group (P=0.106). The two groups had similar rates of adverse events. Conclusions: ETV+TDF combination treatment led to a significantly higher rate of virologic response compared to LAM/ LdT+ADV combination treatment in patients with LAM-resistant HBV who had suboptimal responses to LAM/LdT+ADV regardless of HBV genotypic resistance profile (NCT01597934).
Bibliographical noteFunding Information:
This investigator-initiated trial was supported by an unrestricted grant from Bristol-Myers Squibb (BMS) and clinical research grant from Pusan National University Hospital in 2018. BMS had no role in the study design and the authors retain full responsibility for the collection and interpretation of data, decision to publish, and preparation of the manuscript.
All Science Journal Classification (ASJC) codes
- Molecular Biology