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V(t) = V 0 { A exp (-λ 1 t ) + (1-A) exp(-λ 2 t)}
Viral dynamics during and after entecavir therapy 179
where λ 1 is the slope of the fi rst phase of viral decline, λ 2 is the slope of the second
phase of viral decline, A = (εc – λ 2 ) / (λ 1 -λ 2 ), λ 1/2 = ½ { (c + δ) ± [(c – δ) 2 + 4 (1 – ε) (1-η)cδ]
½ }, V0 is the initial viral load, t is time, d is the death rate of productively infected cells, c
is the clearance rate of the free virus, ε is the effectiveness of entecavir in blocking virion
production from infected cells, and η is the effectiveness of entecavir in blocking de
novo infection of susceptible cells.
The bi-phasic return of virus after withdrawal of therapy was described by application of
a similar bi-phasic model as an inverse image of the bi phasic decline in viral load during
antiviral therapy:
V(t) = V 0 / { A exp (λ 1 t ) + (1-A) exp( - λ 2 t)}
Statistics
Patients were fi tted individually. Due to the small sample size, all patients on entecavir
therapy were evaluated as one group. Non-linear modelling was used to fit both the
bi-phasic model and the inverse bi-phasic model, executed in the PROC NLIN in SAS
6.12. The Mann–Whitney test was used to compare the difference between dose groups
in rebound of viral replication after withdrawal of entecavir. The Kruskal–Wallis test was
applied to calculate the difference in the dose of entecavir with regard to parameters of
viral return. Signifi cant difference was achieved if p