Figure 10. Underlying HBV cccDNA dynamics are unlikely to have a significant outcome on therapeutic outcome.

Simulation of HBV inactivation following 10 doses of therapy given every two weeks. Unlike prior simulations, these simulations assume that DNA cleavage activity accrues evenly over a week rather than instantaneously. Parameters reflect high potency (m*σ = 5, d = 0.004, h = 2). Traces represent no cccDNA activity between does (black lines), residual cccDNA replication between doses at rate = 0.01/day (red lines), hepatocyte replication with dispersion of cccDNA between cells (orange lines) and hepatocyte death with concurrent death of episomes (blue lines). Solid lines are cells with susceptible episomes and would represent therapeutic outcomes in the absence of de novo resistance (Ψ = 0). Dotted lines are cells with resistant episomes and would represent therapeutic outcomes with de novo resistance (Ψ = 0.01). Effects on therapeutic outcomes are minimal unless fairly high levels of cccDNA turnover are assumed (red lines) as may occur in the absence of fully suppressive antiviral therapy.