Two Dynamics Models Of HCV Infection Considering DAAs Treatment

DAAs treatment is of great significance for the treatment of HCV.In this paper,the effects of DAAs treatment on the correlation states of two HCV infection dynam-ics models are investigated.Through theoretical analysis and numerical simulations,some significant results are obtained,which provide some valuable suggestions for the understanding of HCV infection and treatment.In the first chapter,the background knowledge of hepatitis C virus infection and related treatment are briefly introduced,as well as the research status of multiscale hep-atitis C virus infection dynamics model considering treatment.Finally,the main content of this study and the basic theoretical knowledge needed in this paper are summarized.In chapter 2,a kinetic model of the interaction between positive and negative strands of HCV RNA considering DAAs treatment is established.Through Routh-Hurwitz cri-terion and Lyapunov functions construction,it is found that the global dynamic behavior of the model is mainly determined by the basic reproduction number R0,that is,when R0<1,the boundary equilibrium E0 is globally asymptotically stable and the virus is extinct.When R0>1,the positive equilibrium E*is globally asymptotically stable and the virus continues to survive.At the same time,by theoretical analysis and numerical simulations,it is found that when the treatment-related parameter ?s is increased through DAAs treatment,that is,when the rate of virus secretion is decreased,R0 would be in-creased,which might increase the concentration of viral RNA in cells.When making related parameters ??,?r,kt,kc increase,namely reduce Rc and Rm reproduction rate and increase Rt,Rcand Rm degradation rate,will make R0 decrease,which is beneficial to disease control.We also find that DAAs treatment has the greatest effect on the positive strand of HCV RNA used for replication(Rc),and that the change in the replication rate of the positive strand of HCV RNA has the most significant effect on the intracellular RNA concentration.Therefore,we can consider reducing the replication rate of Rc in the treatment to achieve the effect of control and elimination of HCV.In chapter 3,a multiscale dynamics model of HCV infection considering DAAs treatment and humoral immunity is established.Firstly,we use the method of "model aggregation" to transform the PDE model into a mathematically equivalent DDE model.Then the nonnegative and dissipative properties of the DDE system are proved.Second-ly,the existence of equilibria is analyzed,and it is found that according to the difference of basic reproduction number R0 and basic reproduction number of humoral immune response R1,there might be disease-free equilibrium E0,unactivated humoral immune equilibrium E1 and activated humoral immune equilibrium E2 in the system.Then the local and global asymptotic stability of the equilibria is proved,that is,when Ro<1,E0 is globally asymptotically stable.When R1<1<R0,E1 is globally asymptotically stable.When R1>1 and the activation of immune cell delay ?2=0,E2 is globally asymptotically stable.We find that the intracellular delay ?1 of virus secreted by in-fected cells does not affect the stability of the equilibria of the system.However,when?2>0 increases and passes through a certain critical value,the system may undergo periodic oscillation through Hopf branch at E2.Finally,through numerical simulations,it is found that blocking the production of intracellular viral RNA,reducing the secretion of virions,increasing the degradation rate of viral RNA and increasing the intracellular delay of virus secretion in infected cells have positive effects on the control or clearance of HCV.In addition,intercellular infection would increase the difficulty of control or clearance of the virus.At the same time we also find that DAAs treatment by reducing the virion secretion under certain conditions could inhibit the activation of humoral im-munity and lead to the increase of the viral RNA in the cell.Therefore,it is necessary to consider the interaction between DAAs and human immune system when studying and analyzing the effect of HCV DAAs treatment,and it should be paid enough attention in medical practice.In chapter 4,the conclusions of this paper are summarized,and the future problems and directions are pointed out.