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This paper presents and analyzes two mathematical models for the human immunodeficiency virus type-1 (HIV-1) infection with Cytotoxic T Lymphocyte cell (CTL) immune impairment. These models describe the interactions between healthy CD 4 + T cells, latently and actively infected cells, HIV-1 particles, and CTLs. The healthy CD 4 + T cells might be infected when they make contact with: (i) HIV-1 particles due to virus-to-cell (VTC) contact; (ii) latently infected cells due to latent cell-to-cell (CTC) contact; and (iii) actively infected cells due to active CTC contact. Distributed time delays are considered in the second model. We show the nonnegativity and boundedness of the solutions of the systems. Further, we derive basic reproduction numbers ℜ 0 and ℜ ˜ 0 , that determine the existence and stability of equilibria of our proposed systems. We establish the global asymptotic stability of all equilibria by using the Lyapunov method together with LaSalle's invariance principle. We confirm the theoretical results by numerical simulations. The effect of immune impairment, time delay and CTC transmission on the HIV-1 dynamics are discussed. It is found that weak immunity contributes significantly to the development of the disease. Further, we have established that the presence of time delay can significantly decrease the basic reproduction number and then suppress the HIV-1 replication. On the other hand, the presence of latent CTC spread increases the basic reproduction number and then enhances the viral progression. Thus, neglecting the latent CTC spread in the HIV-1 infection model will lead to an underestimation of the basic reproduction number. Consequently, the designed drug therapies will not be accurate or sufficient to eradicate the viruses from the body. These findings may help to improve the understanding of the dynamics of HIV-1 within a host. [ABSTRACT FROM AUTHOR]

In several publications, the dynamical system of HIV and HTLV mono-infections taking into account diffusion, as well as latently infected cells in cellular transmission has been mathematically analyzed. However, no work has been conducted on HTLV/HIV co-infection dynamics taking both factors into consideration. In this paper, a partial differential equations (PDEs) model of HTLV/HIV dual infection was developed and analyzed, considering the cells' and viruses' spatial mobility. CD 4 + T cells are the primary target of both HTLV and HIV. For HIV, there are three routes of transmission: free-to-cell (FTC), latent infected-to-cell (ITC), and active ITC. In contrast, HTLV transmits horizontally through ITC contact and vertically through the mitosis of active HTLV-infected cells. In the beginning, the well-posedness of the model was investigated by proving the existence of global solutions and the boundedness. Eight threshold parameters that determine the existence and stability of the eight equilibria of the model were obtained. Lyapunov functions together with the Lyapunov–LaSalle asymptotic stability theorem were used to investigate the global stability of all equilibria. Finally, the theoretical results were verified utilizing numerical simulations. [ABSTRACT FROM AUTHOR]

In this paper, we formulate a within‐host dynamics model for HIV/HTLV‐I co‐infection under the influence of cytotoxic T lymphocytes (CTLs). The model incorporates silent HIV‐infected CD4+T cells and silent HTLV‐infected CD4+T cells. The model includes two routes of HIV transmission, virus to cell (VTC) and cell to cell (CTC). It also incorporates two modes of HTLV‐I transmission, horizontal transmission via direct CTC contact and vertical transmission through mitotic division of Tax‐expressing HTLV‐infected cells. The model takes into account five types of distributed‐time delays. We analyze the model by proving the nonnegativity and boundedness of the solutions, calculating all possible equilibria, deriving a set of key threshold parameters, and proving the global stability of all equilibria. The global asymptotic stability of all equilibria is established by utilizing Lyapunov function and LaSalle's invariance principle. We present numerical simulations to justify the applicability and effectiveness of the theoretical results. In addition, we discuss the effect of HTLV‐I infection on the HIV dynamics and vice versa. [ABSTRACT FROM AUTHOR]

In this paper, a deterministic model characterizing the within-host infection of Hepatitis C virus (HCV) in intrahepatic and extrahepatic tissues is presented. In addition, the model also includes the effect of the cytotoxic T lymphocyte (CTL) immunity described by a linear activation rate by infected cells. Firstly, the non-negativity and boundedness of solutions of the model are established. Secondly, the basic reproduction number R 01 and immune reproduction number R 02 are calculated, respectively. Three equilibria, namely, infection-free, CTL immune response-free and infected equilibrium with CTL immune response are discussed in terms of these two thresholds. Thirdly, the stability of these three equilibria is investigated theoretically as well as numerically. The results show that when R 01 < 1 , the virus will be cleared out eventually and the CTL immune response will also disappear; when R 02 < 1 < R 01 , the virus persists within the host, but the CTL immune response disappears eventually; when R 02 > 1 , both of the virus and the CTL immune response persist within the host. Finally, a brief discussion will be given. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) and human T-lymphotropic virus type I (HTLV-I) are two retroviruses that infect the susceptible CD 4 + T cells. It is known that HIV and HTLV-I have in common a way of transmission through direct contact with certain body fluids related to infected individuals. Therefore, it is not surprising that a mono-infected person with one of these viruses can be co-infected with the other virus. In the literature, a great number of mathematical models has been presented to describe the within-host dynamics of HIV or HTLV-I mono-infection. However, the within-host dynamics of HIV/HTLV-I co-infection has not been modeled. In this paper, we develop a new within-host HIV/HTLV-I co-infection model. The model includes the impact of Cytotoxic T lymphocytes (CTLs) immune response, which is important to control the progression of viral co-infection. The model describes the interaction between susceptible CD 4 + T cells, silent HIV-infected cells, active HIV-infected cells, silent HTLV-infected cells, Tax-expressing HTLV-infected cells, free HIV particles, HIV-specific CTLs and HTLV-specific CTLs. We first show the nonnegativity and boundedness of the model's solutions and then we calculate all possible equilibria. We derive the threshold parameters which govern the existence and stability of all equilibria of the model. We prove the global asymptotic stability of all equilibria by utilizing Lyapunov function and LaSalle's invariance principle. We have presented numerical simulations to illustrate the effectiveness of our main results. In addition, we discuss the effect of HTLV-I infection on the HIV-infected patients and vice versa. [ABSTRACT FROM AUTHOR]

In the literature, several mathematical models have been formulated and developed to describe the within-host dynamics of either human immunodeficiency virus (HIV) or human T-lymphotropic virus type I (HTLV-I) monoinfections. In this paper, we formulate and analyze a novel within-host dynamics model of HTLV-HIV coinfection taking into consideration the response of cytotoxic T lymphocytes (CTLs). The uninfected CD 4 + T cells can be infected via HIV by two mechanisms, free-to-cell and infected-to-cell. On the other hand, the HTLV-I has two modes for transmission, (i) horizontal, via direct infected-to-cell touch, and (ii) vertical, by mitotic division of active HTLV-infected cells. It is well known that the intracellular time delays play an important role in within-host virus dynamics. In this work, we consider six types of distributed-time delays. We investigate the fundamental properties of solutions. Then, we calculate the steady states of the model in terms of threshold parameters. Moreover, we study the global stability of the steady states by using the Lyapunov method. We conduct numerical simulations to illustrate and support our theoretical results. In addition, we discuss the effect of multiple time delays on stability of the steady states of the system. [ABSTRACT FROM AUTHOR]

In this paper, a mathematical model is formulated to investigate the dynamics of HIV infection. The model incorporates two routes of infection (namely cell-to-cell transmission and virus-to-cell infection), two types of adaptive immune responses (i.e., cellular and antibody immune response) and two intracellular delays (viz., the eclipse phase and virus production period). By constructing Lyapunov functionals, we show that the global dynamics of the model can be explicitly determined by five reproduction numbers. Using the uncertainty and sensitivity analyses, we obtain the mean values and standard deviation of the five reproduction numbers and find that the reproduction numbers are most sensitive to the death rate of infected cells, viral clearance rate and immune parameters. We further compare four related HIV models and show that cell-to-cell transmission, immune responses and time delays can substantially affect the dynamical behavior of the system. Specifically, cell-to-cell transmission increases the concentration of infected cells. Inclusion of cytotoxic T lymphocyte and virus production delay can significantly reduce the viral load and infected cell concentration, and generate a higher level of uninfected CD4+ T cells. The analytical and numerical results may help to improve the understanding of HIV dynamics. [ABSTRACT FROM AUTHOR]

Virus can disseminate between uninfected target cells via two modes, namely, the diffusion-limited cell-free viral spread and the direct cell-to-cell transfer using virological synapses. To examine how these two viral infection modes impact the viral dynamics, in this paper, we propose and analyze a general viral infection model that incorporates these two viral infection modes. The model also includes nonlinear target-cell dynamics, infinitely distributed intracellular delays, nonlinear incidences, and concentration-dependent clearance rates. It is shown that the numbers of secondly infected cells through the cell-free infection mode and the cell-to-cell infection mode both contribute to the basic reproduction number. Under some reasonable assumptions, the model exhibits a global threshold dynamics: the infection is cleared out if the basic reproduction number is less than one and the infection persists if the basic reproduction number is larger than one. Two specific examples are provided to illustrate that our theoretical results cover and improve some existing ones. When the underlying assumptions are not satisfied, oscillations via global Hopf bifurcation can be observed. A brief simulation of two-parameter bifurcation analysis is given to explore the joint impacts on viral dynamics for the interplay between nonlinear target-cell dynamics and intracellular delays. [ABSTRACT FROM AUTHOR]

In this paper we propose and analyze a pathogen dynamics model with antibody and Cytotoxic T Lymphocyte (CTL) immune responses. We incorporate latently infected cells and three distributed time delays into the model. We show that the solutions of the proposed model are nonnegative and ultimately bounded. We derive four threshold parameters which fully determine the existence and stability of the five steady states of the model. Using Lyapunov functionals, we established the global stability of the steady states of the model. The theoretical results are confirmed by numerical simulations. [ABSTRACT FROM AUTHOR]

This paper is devoted to the study of the stability of a CD 4 + T cell viral infection model with diffusion. First, we discuss the well-posedness of the model and the existence of endemic equilibrium. Second, by analyzing the roots of the characteristic equation, we establish the local stability of the virus-free equilibrium. Furthermore, by constructing suitable Lyapunov functions, we show that the virus-free equilibrium is globally asymptotically stable if the threshold value ℛ 0 ≤ 1 ; the endemic equilibrium is globally asymptotically stable if ℛ 0 > 1 and d u ∗ − δ w ∗ ≥ 0. Finally, we give an application and numerical simulations to illustrate the main results. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the dynamical behavior of a nonlinear model for viral infection with Cytotoxic T Lymphocyte (CTL) immune response. The model is a generalization of several models presented in the literature by considering more general functions for the: (i) intrinsic growth rate of uninfected cells; (ii) incidence rate of infection; (iii) natural death rate of infected cells; (iv) rate at which the infected cells are killed by CTL cells; (v) production and removal rates of viruses; (vi) activation and natural death rates of CTLs. We derive two threshold parameters R0 (the basic infection reproduction number) and R1 (the CTL immune response activation number) and establish a set of conditions on the general functions which are sufficient to determine the global dynamics of the model. By using suitable Lyapunov functions and LaSalle's invariance principle, we prove the global asymptotic stability of all equilibria of the model. [ABSTRACT FROM AUTHOR]

Based on some important biological meanings, we propose a class of HIV infection models incorporating both classical cell-free virus diffusion and direct cell-to-cell transmission. According to recent studies, the direct cell-to-cell transfer of HIV is a significantly more efficient mode of retroviral dissemination. In the first part of our analysis, we show that our model possesses non-negative solutions. Then, we derive sufficient conditions for the asymptotic stability of equilibriums. The analytical solutions are verified by simulation results. At the end of the paper, some important conclusions are given. [ABSTRACT FROM AUTHOR]

In this paper, we consider the combined effects of cytotoxic T lymphocyte (CTL) responses on the competition dynamics of two Simian immunodeficiency virus (SIV) strains model. One of strains concerns a relatively slowly replicating and mildly cytopathic virus in the early infection (SIVMneCL8), the other is faster replicating and more cytopathic virus at later stages of the infection (SIVMne170). It is shown that the global dynamics of the ordinary differential equations can be determined by several threshold parameters, and we prove the global stability of the equilibria by rigorous mathematical analysis. To account for a series of infection mechanism leading to viral production, we incorporate time delays in the infection term. Using the methods of constructing suitable Lyapunov functionals and LaSalle’s invariance principle, we obtain the sufficient conditions for the global attractiveness of infection-free equilibrium with both virus strains going extinct, single-infection equilibrium with one of two virus strains out-competing the other one and the two strains coexisting infection equilibrium. We establish that the intracellular delays can destabilize the single-infection equilibrium leading to Hopf bifurcation and periodic oscillations. We show that introduction of immune responses is responsible for the coexistence of two virus strains and the intracellular delays may alter the two-strain competition results. Numerical simulations are presented to illustrate the theoretical conclusions. [ABSTRACT FROM AUTHOR]

The mass action infection law, the most frequently used transmission process in the theoretical studies of disease dynamics, has been challenged in various ways. Hill type infection rate is supposed to be a better alternative to mass action law. In the first phase of this paper, we study a basic HIV model with Hill type infection rate. In the second phase, we modify our basic model with intracellular delay τ that measures the time between the first effective contact between a virus and a healthy CD4 + T cell and the latter becomes productively infective. Mathematical results like well-posedness, permanence, local stability and global stability of both the delayed and non-delayed systems are studied. It is observed that the endemic equilibrium is locally and globally asymptotically stable if the virus replication factor is greater than a threshold value and unstable otherwise. In the latter case, the disease-free steady state occurs and is proved to be globally asymptotically stable. Our simulation results shed different insights on drug therapy when various perturbations are given to the system. It is shown that multi-blockers drug therapy is more appropriate in the treatment of HIV patients in comparison to any mono-blocker drug therapy. [ABSTRACT FROM AUTHOR]

In this paper, we study the global properties of two mathematical models which describe the interaction of the human immunodeficiency virus (HIV) with two classes of target cells, CD4+ T cells and macrophages. The incidence rate of virus infection is given by the Crowley-Martin functional response. The first model has two types of discrete delays while the second one incorporates two types of distributed delays to describe the time needed for infection of cell and virus replication. The basic reproduction number R0 is identified which completely determines the global dynamics of the models. By constructing suitable Lyapunov functionals, we have proven that if R0 ≤ 1 then the uninfected steady state is globally asymptotically stable (GAS), and if R0 > 1 then the infected steady state exists and it is GAS. [ABSTRACT FROM AUTHOR]

In this paper, we study the global analysis of virus dynamics models with discrete delay and with distributed delay. The models describe the interaction of the HIV with two classes of target cells, CD4+ T cells and macrophages. The incidence rate of virus infection is given by the Beddington-DeAngelis functional response. The models have two types of discrete time delay or distributed delay describing the time needed for infection of cell and virus replication. The basic reproduction number R0 is identified which completely determines the global dynamics of the models. By constructing suitable Lyapunov functionals, we have proven that if R0 ≤ 1 then the uninfected steady state is globally asymptotically stable (GAS), and if R0 > 1 then the infected steady state exists and it is GAS. [ABSTRACT FROM AUTHOR]

In this paper, we investigate global dynamics for an in-host HIV-1 infection model with the long-lived infected cells and four intracellular delays. Our model admits two possible equilibria, an uninfected equilibrium and infected equilibrium depending on the basic reproduction number. We derive that the global dynamics are completely determined by the values of the basic reproduction number: if the basic reproduction number is less than one, the uninfected equilibrium is globally asymptotically stable, and the virus is cleared; if the basic reproduction number is larger than one, then the infection persists, and the infected equilibrium is globally asymptotically stable. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we consider an HIV pathogenesis model including cure rate and the full logistic proliferation term of CD4+ T cells in healthy and infected populations. Let be the number of virus released by each productive infected CD4+ T cell. The critical number that ensures the existence of the positive equilibrium is obtained. We further show that if , then there exists a unique uninfected equilibrium point that is locally asymptotically stable. If , then the system is persistent and the only infected steady state is globally asymptotically stable in the feasible region. Numerical simulations are presented to illustrate the obtained main results. Moreover, we find that there exist periodic solutions when the infected steady state is unstable. [Copyright &y& Elsevier]

Abstract: In this paper, a mathematical model for HILV-I infection of CD4+ T-cells is investigated. The force of infection is assumed be of a function in general form, and the resulting incidence term contains, as special cases, the bilinear and the saturation incidences. The model can be seen as an extension of the model [Wang et al. Mathematical analysis of the global dynamics of a model for HTLV-I infection and ATL progression, Math. Biosci. 179 (2002) 207-217; Song, Li, Global stability and periodic solution of a model for HTLV-I infection and ATL progression, Appl. Math. Comput. 180(1) (2006) 401-410]. Mathematical analysis establishes that the global dynamics of T-cells infection is completely determined by a basic reproduction number . If , the infection-free equilibrium is globally stable; if , the unique infected equilibrium is globally stable in the interior of the feasible region. [Copyright &y& Elsevier]

Abstract: It is well-known that the mathematical models provide very important information for the research of human immunodeficiency virus-type 1 and hepatitis C virus (HCV). However, the infection rate of almost all mathematical models is linear. The linearity shows the simple interaction between the T cells and the viral particles. In this paper, we consider the classical mathematical model with non-linear infection rate. The global dynamics of this model is rigorously established. We prove that, if the basic reproduction number , the HIV infection is cleared from the T-cells population; if , the HIV infection persists. Further, the existence of a non-trivial periodic solution is also studied by means of numerical simulation. [Copyright &y& Elsevier]

Abstract: Human T-cell lymphotropic virus I (HTLV-I) infection is linked to the development of adult T-cell leukemia/lymphoma (ATL), among many illness. The healthy CD4+ T cells infect HTLV-I through cell-to-cell contact with infected T-cells. The infected T cells can remain latent and harbor virus for several years before virus production occurs. Actively infected T cells can infect other T cells and can convert to ATL cells, whose growth is assumed to follow a classical logistic growth function. In this paper, we consider the classical mathematical model with saturation response of the infection rate. By stability analysis we obtained the condition for the infected T cells die out and the condition for HTLV-I infection becomes chronic. At the same time, we also obtained the condition for a unique endemic equilibrium is globally stable in the interior of the feasible region. [Copyright &y& Elsevier]

The purpose of this paper is to investigate the qualitative behavior of HIV dynamics models with immune impairment. The HIV particles infect both CD4+ T cells and macrophages. Both latently and actively infected cells are incorporated into the models. The models consider multiple discrete or distributed delays to characterize the time between an HIV contact of an uninfected target cell and the creation of mature HIV. The existence and global stability of the steady states are determined by the basic reproduction number. The global stability analysis of the steady states is performed using Lyapunov method. We solve the system of delay differential equations numerically to support the theoretical results. [ABSTRACT FROM AUTHOR]