TENOFOVIR ALAFENAMIDE FOR MULTIPLE DRUG-RESISTANT CHRONIC HEPATITIS B: A 3-YEAR CLINICAL TRIAL

초록

Background: We recently demonstrated that monotherapy with tenofovir alafenamide (TAF) for 48 weeks showed non-inferior efficacy to tenofovir disoproxil fumarate (TDF) in patients with multiple drug-resistant chronic hepatitis B (CHB). However, the long-term efficacy and safety of prolonged TAF monotherapy in these special population is to be defined. Methods: 174 patients with hepatitis B virus (HBV) resistant to multiple drugs (lamivudine, entecavir, and/or adefovir) under TDF monotherapy for 96 weeks were randomized 1:1 to switch to TAF (n=87) or continue TDF (n=87) for 48 weeks. And then, 172 patients continued TAF (TAF-TAF group; n=87) or switched to TAF (TDF-TAF group; n=85), and completed the 144-week study. Results: In the full analysis set, the proportion of patients with serum HBV DNA <60 IU/mL at week 144 was 98.9% (86/87) in TAF-TAF group and 95.4% (85/87) in TDF-TAF group (P=0.99). Three patients who failed to achieve virological response showed very low level of HBV DNA at week 144 (180, 86, and 149 IU/mL, respectively). No significant difference was observed from baseline in estimated glomerular filtration rate between the two groups at week 144 (0.9% vs -0.9%; P=0.33). Compared with baseline, both TAF-TAF and TDF-TAF groups showed increase in spine bone mineral density at week 144 (3.0 vs 2.1; P=0.21). Total, LDL, and HDL cholesterol levels increased significantly at 24 weeks after switching TDF to TAF in both groups (P<0.001 for all), however, the levels did not increase further during up to 144 weeks of TAF treatment. Conclusion: TAF monotherapy was efficacious and safe for up to 144 weeks, providing sustained virological response in heavily pre-treated patients with multidrug-resistant HBV.