HBV genotype is associated with early (week 12) virologic response during TDF or TAF therapy in patients with chronic hepatitis B
AASLD LiverLearning®. Acharya S. Nov 14, 2016; 144751
Topic: Treatment and Clinical Trials
Subrat Acharya
Subrat Acharya
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TITLE: HBV genotype is associated with early (week 12) virologic response during TDF or TAF therapy in patients with chronic hepatitis B

Gilead Sciences, Inc.

Background: The objective of this study was to determine the impact of host, viral, and treatment-related factors, including HBV genotype, on early virologic suppression after 12 weeks of treatment with TAF, a prodrug of TDF, or TDF.
Methods: The study included adults with CHB enrolled in two Phase 3 studies of TAF 25 mg QD vs. TDF 300 mg QD. The endpoint for this subanalysis was early virologic suppression (HBV DNA <29 IU/mL; Roche COBAS Taqman) at Week 12. The associations between host (age, sex, race, BMI, prior antiviral treatment, and baseline [BL] ALT, FibroTest, and creatinine clearance [CrCl]), viral (HBeAg, BL HBV DNA, HBV genotype), and treatment-related (TAF vs. TDF, adherence) factors with early virologic suppression were determined using logistic regression analyses. Week 48 outcomes were evaluated for patients with or without week 12 viral suppression.
Results: 1,266 of 1,301 randomized subjects (97%) with HBV DNA available at Week 12 were included. The median age was 40 years, 63% were male, 79% were Asian, 23% were treatment-experienced, and 67% received TAF. 66% were HBeAg+, median baseline HBV DNA was 7.4 log10 IU/mL, and HBV genotypes were A (7%), B (19%), C (48%), and D (25%). In total, 72 (6%) and 290 subjects (23%) had HBV DNA <29 IU/mL at Weeks 4 and 12, respectively. The proportion of subjects with HBV DNA suppression at Week 12 was similar between the TAF- and TDF-treated subjects (24% vs. 21%; P=0.434). Unadjusted rates of virologic suppression at Week 12 in subjects with HBV genotypes A, B, C, and D were 19%, 33%, 21%, and 19%, respectively. In a multivariate logistic regression analysis, independent predictors of HBV DNA suppression at Week 12 included HBeAg-negativity at baseline (odds ratio [OR] 3.13; 95% CI 2.12-4.61; P<0.0001), lower viral load (OR per log10 IU/mL: 0.31; 95% CI 0.26-0.37; P<0.0001), higher baseline ALT (OR per U/L: 1.003; 95% CI 1.001-1.006; P=0.004), and HBV genotype B (vs. non-B genotypes: OR 2.26; 95% CI 1.43-3.60; P=0.001). HBV genotype D was associated with a lower likelihood of virologic suppression at Week 12 (vs. non-D genotypes: OR 0.58; 95% CI 0.36-0.92; P=0.021). Compared with patients with HBV DNA ≥29 IU/mL at Week 12, patients with early virologic suppression had higher rates of ALT normalization (42% vs. 49%; P=0.020) and HBeAg loss (13% vs. 22%; P=0.030), but lower median reduction of HBsAg (-0.21 vs. -0.04 IU/mL; P<0.0001) at Week 48.
Conclusions: Early virologic suppression occurs in a minority of patients treated with TAF or TDF and is most frequent in patients with HBV genotype B. Early virologic suppression is also associated with favorable clinical outcomes at Week 48.
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