Understanding the antiviral effects of RNAi-based therapy in HBeAg-positive chronic hepatitis B infection
Sarah Kadelka 1 , Harel Dahari 2 , Stanca M Ciupe 3
Affiliations
Affiliations
1
Department of Mathematics, Virginia Tech, Blacksburg, VA, 24060, USA.
2
Program for Experimental and Theoretical Modeling, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, 60153, USA.
3
Department of Mathematics, Virginia Tech, Blacksburg, VA, 24060, USA. [email protected].
PMID: 33420293 DOI: 10.1038/s41598-020-80594-6
Abstract
The RNA interference (RNAi) drug ARC-520 was shown to be effective in reducing serum hepatitis B virus (HBV) DNA, hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) in HBeAg-positive patients treated with a single dose of ARC-520 and daily nucleosidic analogue (entecavir). To provide insights into HBV dynamics under ARC-520 treatment and its efficacy in blocking HBV DNA, HBsAg, and HBeAg production we developed a multi-compartmental pharmacokinetic-pharamacodynamic model and calibrated it with frequent measured HBV kinetic data. We showed that the time-dependent single dose ARC-520 efficacies in blocking HBsAg and HBeAg are more than 96% effective around day 1, and slowly wane to 50% in 1-4 months. The combined single dose ARC-520 and entecavir effect on HBV DNA was constant over time, with efficacy of more than 99.8%. The observed continuous HBV DNA decline is entecavir mediated, the strong but transient HBsAg and HBeAg decays are ARC-520 mediated. The modeling framework may help assess ongoing RNAi drug development for hepatitis B virus infection. 作者: StephenW 时间: 2021-1-10 17:32
了解基于RNAi的疗法对HBeAg阳性慢性乙型肝炎感染的抗病毒作用
莎拉·卡德卡（Sarah Kadelka）1，哈雷尔·达哈里（Harel Dahari）2，斯坦卡·M·库皮（Stanca M Ciupe）3
隶属关系
隶属关系