Model Of HIV Infection Research Articles

Dynamics Analysis of a Delayed HIV Infection Model with CTL Immune Response and Antibody Immune Response

In this paper, dynamics analysis of a delayed HIV infection model with CTL immune response and antibody immune response is investigated. The model involves the concentrations of uninfected cells, infected cells, free virus, CTL response cells, and antibody antibody response cells. There are three delays in the model: the intracellular delay, virus replication delay and the antibody delay. The basic reproductive number of viral infection, the antibody immune reproductive number, the CTL immune reproductive number, the CTL immune competitive reproductive number and the antibody immune competitive reproductive number are derived. By means of Lyapunov functionals and LaSalle’s invariance principle, sufficient conditions for the stability of each equilibrium is established. The results show that the intracellular delay and virus replication delay do not impact upon the stability of each equilibrium, but when the antibody delay is positive, Hopf bifurcation at the antibody response and the interior equilibrium will exist by using the antibody delay as a bifurcation parameter. Numerical simulations are carried out to justify the analytical results.

In pursuit of sensitivity: Lessons learned from viral nucleic acid detection and quantification on the Raindance ddPCR platform.

Sensitive PCR detection of viral nucleic acids plays a critical role in infectious disease research, diagnosis and monitoring. In the context of SARS-CoV-2 detection, recent reports indicate that digital PCR-based tests are significantly more sensitive than traditional qPCR tests. Numerous factors can influence digital PCR reaction sensitivity. In this review, using a model for human HIV infection and the Raindance ddPCR platform as an example, we describe technical aspects that contribute to sensitive viral signal detection in DNA and RNA from tissue samples, which often harbor viral reservoirs and serve as better predictors of disease outcome and indicators of treatment efficacy.

An analytic study of the fractional order model of HIV-1 virus and CD4+ T-cells using adomian method

In this article, we study the fractional mathematical model of HIV-1 infection of CD4+ T-cells, by studying a system of fractional differential equations of first order with some initial conditions, we study the changing effect of many parameters. The fractional derivative is described in the caputo sense. The adomian decomposition method (Shortly, ADM) method was used to calculate an approximate solution for the system under study. The nonlinear term is dealt with the help of adomian polynomials. Numerical results are presented with graphical justifications to show the accuracy of the proposed methods.

Analysis of time delay model for drug therapy on HIV dynamics

We present and investigate the delayed model of HIV infection for drug therapy. The stability of the equilibrium states, disease free and infected equilibrium states are derived and the existence of Hopf bifurcation analysis is studied. We show that the system is asymptotically stable and the stability is lost in a range due to length of the delay, then Hopf bifurcation occurs when τ exceeds the critical value. At last numerical simulations are provided to verify the theoretical results.

The Notion of Stability of a Differential Equation and Delay Differential Equation Model of HIV Infection of CD4+ T-Cells

This research presents a deep insight to address the notion of stability of an epidemical model of the HIV infection of CD4+ T-Cells. Initially, the stability of an ordinary differential equation (ODE) model is studied. This is followed by studying a delay differential equation (DDE) model the HIV infection of CD4+ T-Cells. The available literature on the stability analysis of the ODE model and the DDE model of the CD4+ T-Cells shows that the stability of the models depends on the basic reproduction number “R0”. Accordingly, for the basic reproduction number R0 <1, the model is asymptotically stable, whereas, for R0 >1, the models are globally stable. This research further studies the stability of the models and address the lower possible stability limits for the infection rate of CD4+ T-Cells with virus and the reproduction rate of infectious CD4+ T-Cells, respectively. Accordingly, the results shows that the lower possible limits for the infection rate of CD4+ T-Cells with virus are 0.0000027 mm-3 and 0.000066 mm-3 for the ODE and DDE models, respectively. Again, the lower stability limits for the reproduction rate of infectious CD4+ T-Cells with virus are 12 mm3day-1 and 273.4 mm3day-1 for the ODE and DDE models, respectively. The research minutely studies the stability of the models and gives a deep insight of the stability of the ODE and DDE models of the HIV infection of CD4+ T-Cells with virus.

Analysis of drug treatment of the fractional HIV infection model of CD4+ T-cells

In this paper we consider fractional order model to HIV infection whose components are plasma densities of uninfected CD4+ T-cells, the infected such cells and the free virus. The main purpose of this work is to study the dynamic of fractional HIV infection of CD4+ T-cells with the impact of drug treatment. An iterative scheme based on the discretization of the domain and short memory principle is proposed to solve fractional HIV infection model numerically. The main reason for using this discretization technique is low computational cost and high accuracy compared to some other methods. Numerical results are presented graphically. Figures are used to show the behaviour of densities of uninfected and infected cells before and after the drug therapy. It is also shown that how the approximate solution varies from fractional order to integer order derivative. By listing CPU time in tabular form efficiency of the iterative scheme is shown. The proposed scheme is also effective in a long time period. The validation of results are shown by comparing results among the proposed technique, Runge Kutta Fourth order method, homotopy perturbation method, homotopy analysis method, Adam-Bashforth predictor-corrector method, Legendre wavelets operational matrix method and Laplace adomian-decomposition method.

Numerical Solution of Fractional Model of HIV-1 Infection in Framework of Different Fractional Derivatives

In this paper, we have extended the model of HIV-1 infection to the fractional mathematical model using Caputo-Fabrizio and Atangana-Baleanu fractional derivative operators. A detailed proof for the existence and the uniqueness of the solution of fractional mathematical model of HIV-1 infection in Atangana-Baleanu sense is presented. Numerical approach is used to find and study the behavior of the solution of the stated model using different derivative operators, and the graphical comparison between the solutions obtained for the Caputo-Fabrizio and the Atangana-Baleanu operator is presented to see which fractional derivative operator is more efficient.

Neuro-optimized numerical treatment of HIV infection model

In this paper, a neuro-optimized numerical method is presented for approximation of HIV virus progression model in the human body. The model is composed of coupled nonlinear system of differential equations (DEs) containing healthy and infected T-Cells and HIV free virus particles. The coupled system is transformed into feedforward artificial neural network (ANN) with Mexican hat wavelet function in the hidden layers. Two meta-heuristic algorithms based on chaotic particle swarm optimization (CPSO) and its hybrid version with local search technique are exploited to tune the parameters of ANN in an unsupervised manner of error function. A comprehensive testbed is established to observe the virus growth per day with performance metric containing fitness value, computational time complexity and convergence. The proposed solutions are compared with state of art Runge–Kutta method and Legendre Wavelet Collocation Method (LWCM). The core advantages of the proposed scheme are getting the solution on continuous grid, consistent convergence, simplicity in implementation and handling strong nonlinearity effectively.

Fractional Order Modification of Tuckwell and Wan Medical Model

A fractional order modification of Tuckwell and Wan for HIV-1 model is given. Tuckwell and Wan gave a model for HIV-1 infection of CD4+T-cells and solving. The number of CD4+T-cellsgained by the solution of the tth equation decreases with time which is a main weak point in this model. So we give a modification for their model in a fractional differential from. The results of solution are compared with the results of the other solutions methods.

Dynamics of an HIV pathogenesis Model with Absorption and Saturation Incidence

In this paper, the dynamics of an HIV infection model with absorption and saturation incidence are proposed and analyzed. Further, we introduce a time delay to the model, which describes a time between infected cells and excretion of the viral particles. This model is used to explain existence, characteristic equations, and stability of infected and disease free steady states. Numerical simulations are provided to illustrate the theoretical results.

Development of a reverse transcription droplet digital PCR (RT-ddPCR) assay for sensitive detection of simian immunodeficiency virus (SIV)

BackgroundSimian immunodeficiency virus (SIV)-infected rhesus macaques constitute an excellent model of human HIV infection. Sensitive detection of SIV RNA in cell and tissue samples from infected animals subjected to treatment regimens becomes especially critical in determining which therapeutic attempts are successful, and consequently, which interventions should be prioritized in HIV cure research.ResultsIn this report, we describe the design and testing of a Raindance ddPCR platform-based, sensitive SIV reverse transcription droplet digital PCR (RT-ddPCR) assay by exploring the combinations of various priming conditions and reverse transcriptases, and testing one-step vs. two-step procedures, to eliminate background signal(s) and enable detection and quantification of low level target signals.ConclusionsSimilar reaction conditions and assay validation procedures can be explored for potential development of additional assays for other applications that require sensitive detection of low-level targets in RNA samples.

Stability and Hopf bifurcation of a CTL-inclusive HIV-1 infection model with both viral and cellular infections, and three delays

Abstract In this paper, we assess the viral dynamics of a HIV-1 mathematical model that incorporates virus-to-cell and cell-to-cell transmissions, CTL response immune and three delays describing intracellular delays and immune response delay. The model includes a constant production rate of CTLs export from thymus. Our focus is on the effect of three delays on the infection dynamics. The basic reproduction number, R 0 , which depends on the intracellular delay, is shown to determine stability conditions of the model steady states. Employing a suitable Lyapunov function, we show that the infection-free equilibrium is globally asymptotically stable including the three time delays when the basic reproduction number is a smaller amount than one. Additionally, for the special case where there is no immune delay in the model, the global stability of the unique endemic equilibrium is also established (using suitable Lyapunov functions) whenever R 0 is larger than one. Furthermore, we study the local and hopf bifurcation of the endemic equilibrium in general case with all delays being positive. When the three delays are positive, we determine some conditions for stability switches of the endemic equilibrium by using the immune delay as a bifurcation parameter. Numerical simulations indicate that an increase of the immune delay can stabilize and/or destabilize the endemic equilibrium.

Analysis and control of a delayed HIV infection model with cell‐to‐cell transmission and cytotoxic T lymphocyte immune response

Recent researches show that virus‐to‐cell infection and cell‐to‐cell transmission are two HIV infection modes. In this paper, we propose a delayed HIV infection model including both virus‐to‐cell infection and cell‐to‐cell transmission and cytotoxic T lymphocyte immune response. The time delay describes the phenomenon between viral entry and viral production. We show the nonnegativity and boundedness of solution, obtain the steady states, and prove local asymptotic stability of the steady states. Then the optimal control problem with antiretroviral therapy and pharmacological delay is posed. We establish and analyze two types of objective functions: one is linear control and the other is quadratic control. Numerical simulations have been performed to verify the stability of steady states and show the optimal control strategies and the effects of control on cells concentration by Matlab and Lingo.

Inhibition of HIV-1 gene transcription by KAP1 in myeloid lineage

HIV-1 latency generates reservoirs that prevent viral eradication by the current therapies. To find strategies toward an HIV cure, detailed understandings of the molecular mechanisms underlying establishment and persistence of the reservoirs are needed. The cellular transcription factor KAP1 is known as a potent repressor of gene transcription. Here we report that KAP1 represses HIV-1 gene expression in myeloid cells including microglial cells, the major reservoir of the central nervous system. Mechanistically, KAP1 interacts and colocalizes with the viral transactivator Tat to promote its degradation via the proteasome pathway and repress HIV-1 gene expression. In myeloid models of latent HIV-1 infection, the depletion of KAP1 increased viral gene elongation and reactivated HIV-1 expression. Bound to the latent HIV-1 promoter, KAP1 associates and cooperates with CTIP2, a key epigenetic silencer of HIV-1 expression in microglial cells. In addition, Tat and CTIP2 compete for KAP1 binding suggesting a dynamic modulation of the KAP1 cellular partners upon HIV-1 infection. Altogether, our results suggest that KAP1 contributes to the establishment and the persistence of HIV-1 latency in myeloid cells.

Stability of a general adaptive immunity HIV infection model with silent infected cell-to-cell spread

This paper proposes and analyzes an adaptive immunity HIV infection model. The model describes the interaction between healthy CD 4 + T cells, silent (latent) infected cells, active infected cells, free HIV particles, Cytotoxic T lymphocytes (CTLs) and antibodies. The healthy CD 4 + T cells can be infected when they are contacted by one of the following: (i) free HIV particles, and this is known as virus-to-cell (VTC) transmission (ii) silent infected cells, and we call this mode of infection as silent HIV-infected cell-to-cell (CTC) transmission, and (iii) active infected cells, and we call this mechanism active HIV-infected CTC transmission. The incidence rates of the healthy CD 4 + T cells with free HIV particles, silent infected cells, and active infected cells are given by general functions. Moreover, the production/proliferation and removal/death rates of all compartments are represented by general functions. The model is an improvement of the existing HIV infection models which have neglected the incidence between the silent infected cells and healthy CD 4 + T cells. We first show that the model is well-posed. Then, we show that the model has five equilibria and their existence are governed by five threshold parameters. Under a set of conditions on the general functions and the threshold parameters, we have proven the global asymptotic stability of all equilibria by using Lyapunov’s method. We have illustrated the theoretical results via numerical simulations. We have studied the effect of CTC transmission on the dynamical behavior of the system. We have shown that inclusion of CTC transmission decreases the concentration of the healthy CD4 + T cells and increases the concentrations of the infected cells and free HIV particles.

A Rat Model of EcoHIV Brain Infection.

It has been well studied that the EcoHIV infected mouse model is of significant utility in investigating HIV associated neurological complications. Establishment of the EcoHIV infected rat model for studies of drug abuse and neurocognitive disorders, would be beneficial in the study of neuroHIV and HIV-1 associated neurocognitive disorders (HAND). In the present study, we demonstrate the successful creation of a rat model of active HIV infection using chimeric HIV (EcoHIV). First, the lentiviral construct of EcoHIV was packaged in cultured 293 FT cells for 48 hours. Then, the conditional medium was concentrated and titered. Next, we performed bilateral stereotaxic injections of the EcoHIV-EGFP into F344/N rat brain tissue. One week after infection, EGFP fluorescence signals were detected in the infected brain tissue, indicating that EcoHIV successfully induces an active HIV infection in rats. In addition, immunostaining for the microglial cell marker, Iba1, was performed. The results indicated that microglia were the predominant cell type harboring EcoHIV. Furthermore, EcoHIV rats exhibited alterations in temporal processing, a potential underlying neurobehavioral mechanism of HAND as well as synaptic dysfunction eight weeks after infection. Collectively, the present study extends the EcoHIV model of HIV-1 infection to the rat offering a valuable biological system to study HIV-1 viral reservoirs in the brain as well as HAND and associated comorbidities such as drug abuse.

Global Exponential Stability of a Delayed HIV Infection Model with a Nonlinear Incidence Rate

Under the assumption that there is a time delay between the time target cells are contacted by the virus particles and the time the contacted cells become actively infected, we investigate the exponential stability of the noninfected equilibrium for a delayed HIV infection model with a nonlinear incidence rate. Compared with the global asymptotic stability analysis based on basic reproduction number, exponential stability analysis reveals the change range of various cells in different time periods.

Stem cell-derived CAR T cells traffic to HIV reservoirs in macaques.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) with CCR5– donor cells is the only treatment known to cure HIV-1 in patients with underlying malignancy. This is likely due to a donor cell–mediated graft-versus-host effect targeting HIV reservoirs. Allo-HSCT would not be an acceptable therapy for most people living with HIV due to the transplant-related side effects. Chimeric antigen receptor (CAR) immunotherapies specifically traffic to malignant lymphoid tissues (lymphomas) and, in some settings, are able to replace allo-HSCT. Here, we quantified the engraftment of HSC-derived, virus-directed CAR T cells within HIV reservoirs in a macaque model of HIV infection, using potentially novel IHC assays. HSC-derived CAR cells trafficked to and displayed multilineage engraftment within tissue-associated viral reservoirs, persisting for nearly 2 years in lymphoid germinal centers, the brain, and the gastrointestinal tract. Our findings demonstrate that HSC-derived CAR+ cells reside long-term and proliferate in numerous tissues relevant for HIV infection and cancer.

Stability and bifurcation analysis of an HIV-1 infection model with a general incidence and CTL immune response

In this paper, with eclipse stage in consideration, we propose an HIV-1 infection model with a general incidence rate and CTL immune response. We first study the existence and local stability of equilibria, which is characterized by the basic infection reproduction number and the basic immunity reproduction number . The local stability analysis indicates the occurrence of transcritical bifurcations of equilibria. We confirm the bifurcations at the disease-free equilibrium and the infected immune-free equilibrium with transmission rate and the decay rate of CTLs as bifurcation parameters, respectively. Then we apply the approach of Lyapunov functions to establish the global stability of the equilibria, which is determined by the two basic reproduction numbers. These theoretical results are supported with numerical simulations. Moreover, we also identify the high sensitivity parameters by carrying out the sensitivity analysis of the two basic reproduction numbers to the model parameters.

Dynamics of a delayed integro-differential HIV infection model with multiple target cells and nonlocal dispersal

In this paper, we formulate an age-space-structured HIV infection model that incorporating infection age, multiple target cells, and nonlocal dispersal. Applying the characteristic line method, we reduce the infection-age model to a delayed integro-differential system. The global well-posedness and boundedness of the semiflow for the system are established. The principal eigenvalue of the nonlocal dispersal problem is formulated, and it plays the same role as the basic reproduction number $$R_0$$ (the spectral radius of the next generation operator), which determines the global behavior of the steady states of the system. More precisely, the infection-free steady state is globally asymptotically stable (g.a.s) when $$R_0<1$$ , the virus is always present and the infected steady state is g.a.s when $$R_0>1$$ . Numerical simulations are carried out reinforcing these analytical results. In particular, three different kernel functions are given out to study the impact of dispersal form on the HIV infection within the host. Finally, our simulation works show that (i) increasing the dispersal rate and decreasing the intracellular delay will be increasing the final viral loads; (ii) the dispersal kernel function affects the value of $$R_0$$ and the final viral loads, and it is revealed that the dispersal form plays a crucial role in the process of HIV infection within the host.