Hopf Bifurcation and Stability of Periodic Solutions for Delay Differential Model of HIV Infection of CD4 +

This paper deals with stability and Hopf bifurcation analyses of a mathematical model of HIV infection of CD4+ T-cells. The model is based on a system of delay differential equations with logistic growth term and antiretroviral treatment with a discrete time delay, which plays a main role in changing the stability of each steady state. By fixing the time delay as a bifurcation parameter, we get a limit cycle bifurcation about the infected steady state. We study the effect of the time delay on the stability of the endemically infected equilibrium. We derive explicit formulae to determine the stability and direction of the limit cycles by using center manifold theory and normal form method. Numerical simulations are presented to illustrate the results

Study of Virus Dynamics by Mathematical Models

This thesis studies virus dynamics within host by mathematical models, and topics discussed include viral release strategies, viral spreading mechanism, and interaction of virus with the immune system. Firstly, we propose a delay differential equation model with distributed delay to investigate the evolutionary competition between budding and lytic viral release strategies. We find that when antibody is not established, the dynamics of competition depends on the respective basic reproduction numbers of the two viruses. If the basic reproductive ratio of budding virus is greater than that of lytic virus and one, budding virus can survive. When antibody is established for both strains but the neutralization capacities are the same for both strains, consequence of the competition also depends only on the basic reproduction numbers of the budding and lytic viruses. Using two concrete forms of the viral production functions, we are also able to conclude that budding virus will outcompete if the rates of viral production, death rates of infected cells and neutralizing capacities of the antibodies are the same for budding and lytic viruses. In this case, budding strategy would have evolutionary advantage. However, if the antibody neutralization capacity for the budding virus is larger than that for the lytic virus, lytic virus can outcompete provided that its reproductive ratio is very high. An explicit threshold is derived. Secondly, we consider model containing two modes for viral infection and spread, one is the diffusion-limited free virus transmission and the other is the direct cell-to-cell transfer of viral particles. By incorporating infection age, a rigorous analysis of the model shows that the model demonstrates a global threshold dynamics, fully described by the basic reproduction number, which is identified explicitly. The formula for the basic reproduction number of our model reveals the effects of various model parameters including the transmission rates of the two modes, and the impact of the infection age. We show that basic reproduction number is underestimated in the existing models that only consider the cell-free virus transmission, or the cell-to-cell infection, ignoring the other. Assuming logistic growth for target cells, we find that if the basic reproduction number is greater than one, the infection can persist and Hopf bifurcation can occur from the positive equilibrium within certain parameter ranges. Thirdly, the repulsion effect of superinfecting virion by infected cells is studied by a reaction diffusion equation model for virus infection dynamics. In this model, the diffusion of virus depends not only on its concentration gradient but also on the concentration of infected cells. The basic reproduction number, linear stability of steady states, spreading speed, and existence of traveling wave solutions for the model are discussed. It is shown that viruses spread more rapidly with the repulsion effect of infected cells on superinfecting virions, than with random diffusion only. For our model, the spreading speed of free virus is not consistent with the minimal traveling wave speed. With our general model, numerical computations of the spreading speed shows that the repulsion of superinfecting vision promotes the spread of virus, which confirms, not only qualitatively but also quantitatively, some recent experimental results. Finally, the effect of chemotactic movement of CD8+ cytotoxic T lymphocytes (CTLs) on HIV-1 infection dynamics is studied by a reaction diffusion model with chemotaxis. Choosing a typical chemosensitive function, we find that chemoattractive movement of CTLs due to HIV infection does not change stability of the positive steady state of the model. However, chemorepulsion movement of CTLs destabilizes the positive steady state as the strength of the chemotactic sensitivity increases. In this case, Turing instability occurs, which can be Hopf bifurcation or steady state bifurcation, and spatial heterogeneous patterns may form

Modelling the Drugs Therapy for HIV Infection with Discrete-Time Delay

A discrete-time-delay differential mathematical model that described HIV infection of CD4+ T cells with drugs therapy is analyzed. The stability of the two equilibria and the existence of Hopf bifurcation at the positive equilibrium are investigated. Using the normal form theory and center manifold argument, the explicit formulas which determine the stability, the direction, and the period of bifurcating periodic solutions are derived. Numerical simulations are carried out to explain the mathematical conclusions

Study of an HIV-1 Model with Time Delays

We propose a mathematical model for HIV-1 infection with two time delays, one for the average latent period of cell infection and the other for the average time needed for the virus production after a virion enters a cell. The model examines a viral-therapy for controlling infections through recombining HIV-1 virus with a genetically modified virus. When only the intracellular delay is enrolled into model (1.13), the basic reproduction numbers Rq and Rd are identified and their threshold properties are discussed. When Rq \u3c 1, the infection-free equilibrium Eq is globally asymptotically stable. When Rq \u3e 1, Eq becomes unstable and there occurs the single-infection equilibrium Es. If Rq \u3e 1 and Rd \u3c 1, Es is asymptotically stable, while for Rd \u3e 1, Es loses its stability to the double-infection equilibrium. For the double-infection equilibrium Ed, we show how to determine its stability and existence of Hopf bifurcation. Some simulations are presented to demonstrate the theoretical results. Further investigation is carried over by introducing the second time lag into model (2.1). We have identified the new basic reproduction numbers Rqand Rd, and proved that for Rq \u3c 1 the infection-free equilibrium Eq is globally asymptotically stable. If Rq \u3e 1 and Rd \u3c 1, the single-infection equilibrium Es is asymptotically stable. For the double-infection equilibrium Ed, it has been found that there exist both Hopf and N double Hopf bifurcations. These theoretical predictions are verified by using some numerical examples. Evidences indicate that the viral-therapy, of recombining HIV-1 virus with a genetically modified virus may be effective in reducing the HIV-1 load, and larger delays may be able to help eradicate the virus

Bifurcations and multistability in a model of cytokine-mediated autoimmunity

This paper investigates the dynamics of immune response and autoimmunity with particular emphasis on the role of regulatory T cells (Tregs), T cells with different activation thresholds, and cytokines in mediating T cell activity. Analysis of the steady states yields parameter regions corresponding to regimes of normal clearance of viral infection, chronic infection, or autoimmune behavior, and the boundaries of stability and bifurcations of relevant steady states are found in terms of system parameters. Numerical simulations are performed to illustrate different dynamical scenarios, and to identify basins of attraction of different steady states and periodic solutions, highlighting the important role played by the initial conditions in determining the outcome of immune interactions

Dynamic analysis of a fractional-order SIRS model with time delay

Mathematical modeling plays a vital role in the epidemiology of infectious diseases. Policy makers can provide the effective interventions by the relevant results of the epidemic models. In this paper, we build a fractional-order SIRS epidemic model with time delay and logistic growth, and we discuss the dynamical behavior of the model, such as the local stability of the equilibria and the existence of Hopf bifurcation around the endemic equilibrium. We present the numerical simulations to verify the theoretical analysis