These reductions were similar in magnitude and duration of effect to those observed in the mouse HBV models receiving similar doses. The efficacy and click here safety of ARC-520 in a large primate demonstrate its promise as
a new class of therapeutic for patients chronically infected with HBV. HBsAg in chimpanzee Disclosures: Robert E. Lanford – Grant/Research Support: Arrowhead Research Christine I. Wooddell – Employment: Arrowhead Research Corporation Qili Chu – Employment: Arrowhead Madison Bruce Given – Board Membership: Icon plc, Calando Pharmaceuticals; Consulting: Leonardo Biosystems, Inc; Employment: Arrowhead Research Corp David L. Lewis – Employment: Arrowhead Research Corporation The following people have nothing to disclose: Deborah Chavez, Claudia Oropeza, Holly L. Hamilton, Alan McLachlan, Christopher R. Anzalone Background/Aims: Previous analyses demonstrated lower genetic distance within HBV polymerase/reverse transcriptase (pol/RT) and HBsAg genes in HBeAg+ GT A and D CHB subjects who lost HBsAg compared to control subjects who maintained high HBsAg levels through 192 weeks of TDF treatment. This study evaluated the differences in mean pairwise genetic distance across the core and HBx genes in this subject cohort. Methods: Study GS-US-174-0103 HBeAg+ subjects
were randomized 2:1 to receive TDF or ADV for 48 weeks followed by open-label TDF. After 4 years, 23/266 (8.6%) experienced HBsAg loss, including 14 GT A and 7 GT D subjects. 17 GT A and 10 GT D subjects selleck products who maintained high HBsAg levels with similar baseline HBV DNA and ALT were selected as case controls. Population sequencing was performed on baseline samples and pair-wise genetic distance matrices for segments across HBx and core genes were used to calculate viral diversity. Non-parametric Levene test for homogeneity of variances in control and HBsAg loss groups was performed for each region, and equality of mean genetic distances within regions was evaluated using the Mann-Whitney-Wilcoxon test. The Hochberg
procedure was used to control for multiple testing. Results: For GT A and GT D, in general, segments corresponding to non structural regulatory elements (URR, NRE, CURS, and EnhII within HBx gene and precore) showed higher viral diversity within HBsAg loss patients compared 上海皓元医药股份有限公司 to controls. In contrast, the core gene, which encodes a structural element, the opposite pattern was observed with lower viral diversity in HBsAg loss patients. Similar to previous observations across the pol/RT and HBsAg genes, genotype-specific differences were observed across the core and HBx genes. For GT A, 6/9 segments had significant genetic diversity differences between HBsAg loss and control subjects, while only 4/9 segments had significant differences for GT D. In addition, GT A subjects had lower mean pairwise genetic distance in the majority of HBx and core gene segments evaluated compared to GT D subjects.