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This paper formulates and analyzes two mathematical models that describe the within-host dynamics of human immunodeficiency virus type 1 (HIV-1) with impairment of both cytotoxic T lymphocytes (CTLs) and B cells. Both viral transmission (VT) and cellular infection (CT) mechanisms are considered. The second model is a generalization of the first model that includes distributed time delays. For the two models, we establish the non-negativity and boundedness of the solutions, find the basic reproductive numbers, determine all possible steady states and establish the global asymptotic stability properties of all steady states by means of the Lyapunov method. We confirm the theoretical results by conducting numerical simulations. We conduct a sensitivity analysis to show the effect of the values of the parameters on the basic reproductive number. We discuss the results, showing that impaired B cells and CTLs, time delay and latent CT have significant effects on the HIV-1 dynamics. [ABSTRACT FROM AUTHOR]

Significant and composite indices for infectious disease can have implications for developing interventions and public health. This paper presents an investment for developing access to further analysis of the incidence of individual and multiple diseases. This research mainly comprises two steps: first, an automatic and reproducible procedure based on functional data analysis techniques was proposed for analyzing the dynamic properties of each disease; second, orthogonal transformation was adopted for the development of composite indices. Between 2000 and 2019, nineteen class B notifiable diseases in China were collected for this study from the National Bureau of Statistics of China. The study facilitates the probing of underlying information about the dynamics from discrete incidence rates of each disease through the procedure, and it is also possible to obtain similarities and differences about diseases in detail by combining the derivative features. There has been great success in intervening in the majority of notifiable diseases in China, like bacterial or amebic dysentery and epidemic cerebrospinal meningitis, while more efforts are required for some diseases, like AIDS and virus hepatitis. The composite indices were able to reflect a more complex concept by combining individual incidences into a single value, providing a simultaneous reflection for multiple objects, and facilitating disease comparisons accordingly. For the notifiable diseases included in this study, there was superior management of gastro-intestinal infectious diseases and respiratory infectious diseases from the perspective of composite indices. This study developed a methodology for exploring the prevalent properties of infectious diseases. The development of effective and reliable analytical methods provides special insight into infectious diseases' common dynamics and properties and has implications for the effective intervention of infectious diseases. [ABSTRACT FROM AUTHOR]

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]

Taking into account the effects of the heterogeneity of the population and media coverage on disease transmission, in this paper, a hybrid HIV/AIDS model with age-structure, self-protection awareness and media coverage is formulated, which is made up of five partial differential equations (PDEs) and one ordinary differential equation (ODE). We establish the existence of the solution associated with the hybrid system and prove that the solution is unique, bounded and positive utilizing the semigroup approach. Based on the basic reproduction number R 0 , the threshold dynamics of this model are rigorously investigated, that is, there always is a unique disease-free steady state E 0 and it is globally stable when R 0 < 1 , that is, the disease dies out. Further, there exists a unique endemic steady state E * and it is locally stable when R 0 > 1 and some additional technical conditions are met. In addition, the uniform persistence of this hybrid system is demonstrated for R 0 > 1 , which means that the disease remains at the endemic level for a long time, which is not discussed in other age-structured infectious disease articles. Numerical simulations are also given to explain the main theoretical results, which suggest that age variability is a non-negligible factor in HIV/AIDS transmission, that is, the moment and scale of HIV/AIDS outbreaks are diverse for people of different ages, and media coverage can encourage people to take steps to avoid potential infection and control the spread of the disease. [ABSTRACT FROM AUTHOR]

The HIV/AIDS epidemic is still active worldwide with no existing definitive cure. Based on the WHO recommendations stated in 2014, a treatment, called Pre-Exposure Prophylaxis (PrEP), has been used in the world, and more particularly in France since 2016, to prevent HIV infections. In this paper, we propose a new compartmental epidemiological model with a limited protection time offered by this new treatment. We describe the PrEP compartment with an age-structure hyperbolic equation and introduce a differential equation on the parameter that governs the PrEP starting process. This leads us to a nonlinear differential–difference system with discrete delay. After a local stability analysis, we prove the global behavior of the system. Finally, we illustrate the solutions with numerical simulations based on the data of the French Men who have Sex with Men (MSM) population. We show that the choice of a logistic time dynamics combined with our Hill-function-like model leads to a perfect data fit. These results enable us to forecast the evolution of the HIV epidemics in France if the populations keep using PrEP. [ABSTRACT FROM AUTHOR]

In recent decades, AIDS has been one of the main challenges facing the medical community around the world. Due to the large human deaths of this disease, researchers have tried to study the dynamic behaviors of the infectious factor of this disease in the form of mathematical models in addition to clinical trials. In this paper, we study a new mathematical model in which the dynamics of CD 4 + T-cells under the effect of HIV-1 infection are investigated in the context of a generalized fractal-fractional structure for the first time. The kernel of these new fractal-fractional operators is of the generalized Mittag-Leffler type. From an analytical point of view, we first derive some results on the existence theory and then the uniqueness criterion. After that, the stability of the given fractal-fractional system is reviewed under four different cases. Next, from a numerical point of view, we obtain two numerical algorithms for approximating the solutions of the system via the Adams-Bashforth method and Newton polynomials method. We simulate our results via these two algorithms and compare both of them. The numerical results reveal some stability and a situation of lacking a visible order in the early days of the disease dynamics when one uses the Newton polynomial. [ABSTRACT FROM AUTHOR]

In this study, we consider a system of nonlinear differential equations modeling the human immunodeficiency virus type-1 (HIV-1) in a variable environment. Infected cells were subdivided into two compartments describing both latently and productively infected cells. Thus, three routes of infection were considered including the HIV-to-cell contact, latently infected cell-to-cell contact, and actively infected cell-to-cell contact. The nonnegativity and boundedness of the trajectories of the dynamics were proved. The basic reproduction number was determined through an integral operator. The global stability of steady states is then analyzed using the Lyapunov theory together with LaSalle's invariance principle for the case of a fixed environment. Similarly, for the case of a variable environment, we showed that the virus-free periodic solution is globally asymptotically stable once R 0 ≤ 1 , while the virus will persist once R 0 > 1 . Finally, some numerical examples are provided illustrating the theoretical investigations. [ABSTRACT FROM AUTHOR]

In this paper, we propose a six-dimensional nonlinear system of differential equations for the human immunodeficiency virus (HIV) including the B-cell functions with a general nonlinear incidence rate. The compartment of infected cells was subdivided into three classes representing the latently infected cells, the short-lived productively infected cells, and the long-lived productively infected cells. The basic reproduction number was established, and the local and global stability of the equilibria of the model were studied. A sensitivity analysis with respect to the model parameters was undertaken. Based on this study, an optimal strategy is proposed to decrease the number of infected cells. Finally, some numerical simulations are presented to illustrate the theoretical findings. [ABSTRACT FROM AUTHOR]

Multivariate "Bayesian" regression via a shared component model has gained popularity in recent years, particularly in modeling and mapping the risks associated with multiple diseases. This method integrates joint outcomes, fixed effects of covariates, and random effects involving spatial and temporal components and their interactions. A shared spatial–temporal component considers correlations between the joint outcomes. Notably, due to spatial–temporal variations, certain covariates may exhibit nonlinear effects, necessitating the use of semiparametric regression models. Sometimes, choropleth maps based on regional data that is aggregated by administrative regions do not adequately depict infectious disease transmission. To counteract this, we combine the area-to-point geostatistical model with inverse distance weighted (IDW) interpolation for high-resolution mapping based on areal data. Additionally, to develop an effective and efficient early warning system for controlling disease transmission, it is crucial to forecast disease risk for a future time. Our study focuses on developing a novel multivariate Bayesian semiparametric regression model for forecasting and mapping HIV and TB risk in West Java, Indonesia, at fine-scale resolution. This novel approach combines multivariate Bayesian semiparametric regression with geostatistical interpolation, utilizing population density and the Human Development Index (HDI) as risk factors. According to an examination of annual data from 2017 to 2021, HIV and TB consistently exhibit recognizable spatial patterns, validating the suitability of multivariate modeling. The multivariate Bayesian semiparametric model indicates significant linear effects of higher population density on elevating HIV and TB risks, whereas the impact of the HDI varies over time and space. Mapping of HIV and TB risks in 2022 using isopleth maps shows a clear HIV and TB transmission pattern in West Java, Indonesia. [ABSTRACT FROM AUTHOR]

In this paper, we study possibilities of eradication of populations at an early stage of a patient's infection in the framework of the seven-order Stengel model with 11 model parameters and four treatment parameters describing the interactions of wild-type and mutant HIV particles with various immune cells. We compute ultimate upper bounds for all model variables that define a polytope containing the attracting set. The theoretical possibility of eradicating HIV-infected populations has been investigated in the case of a therapy aimed only at eliminating wild-type HIV particles. Eradication conditions are expressed via algebraic inequalities imposed on parameters. Under these conditions, the concentrations of wild-type HIV particles, mutant HIV particles, and infected cells asymptotically tend to zero with increasing time. Our study covers the scope of acceptable therapies with constant concentrations and values of model parameters where eradication of infected particles/cells populations is observed. Sets of parameter values for which Stengel performed his research do not satisfy our local asymptotic stability conditions. Therefore, our exploration develops the Stengel results where he investigated using the optimal control theory and numerical dynamics of his model and came to a negative health prognosis for a patient. The biological interpretation of these results is that after a sufficiently long time, the concentrations of wild-type and mutant HIV particles, as well as infected cells will be maintained at a sufficiently low level, which means that the viral load and the concentration of infected cells will be minimized. Thus, our study theoretically confirms the possibility of efficient treatment beginning at the earliest stage of infection. Our approach is based on a combination of the localization method of compact invariant sets and the LaSalle theorem. [ABSTRACT FROM AUTHOR]

Human T-lymphotropic virus type I (HTLV-I) and human immunodeficiency virus (HIV) are two famous retroviruses that share similarities in their genomic organization, and differ in their life cycle as well. It is known that HTLV-I and HIV have in common a way of transmission via direct contact with certain body fluids related to infected patients. Thus, it is not surprising that a single-infected person with one of these viruses can be dually infected with the other virus. In the literature, many researchers have devoted significant efforts for modeling and analysis of HTLV or HIV single infection. However, the dynamics of HTLV/HIV dual infection has not been formulated. In the present paper, we formulate an HTLV/HIV dual infection model. The model includes the impact of the Cytotoxic T lymphocyte (CTLs) immune response, which is important to control the dual infection. The model describes the interaction between uninfected CD 4 + T cells, HIV-infected cells, HTLV-infected cells, free HIV particles, HIV-specific CTLs, and HTLV-specific CTLs. We establish that the solutions of the model are non-negative and bounded. We calculate all steady states of the model and deduce the threshold parameters which determine the existence and stability of the steady states. We prove the global asymptotic stability of all steady states by utilizing the Lyapunov function and Lyapunov–LaSalle asymptotic stability theorem. We solve the system numerically to illustrate the our main results. In addition, we compared between the dynamics of single and dual infections. [ABSTRACT FROM AUTHOR]

In this paper, we construct an Human immunodeficiency virus (HIV) dynamics model with impairment of B-cell functions and the general incidence rate. We incorporate three types of infected cells, (i) latently-infected cells, which contain the virus, but do not generate HIV particles, (ii) short-lived productively-infected cells, which live for a short time and generate large numbers of HIV particles, and (iii) long-lived productively-infected cells, which live for a long time and generate small numbers of HIV particles. The model considers five distributed time delays to characterize the time between the HIV contact of an uninfected CD4 + T-cell and the creation of mature HIV. The nonnegativity and boundedness of the solutions are proven. The model admits two equilibria, infection-free equilibrium E P 0 and endemic equilibrium E P 1 . We derive the basic reproduction number R 0 , which determines the existence and stability of the two equilibria. The global stability of each equilibrium is proven by utilizing the Lyapunov function and LaSalle's invariance principle. We prove that if R 0 < 1 , then E P 0 is globally asymptotically stable, and if R 0 > 1 , then E P 1 is globally asymptotically stable. These theoretical results are illustrated by numerical simulations. The effect of impairment of B-cell functions, time delays, and antiviral treatment on the HIV dynamics are studied. We show that if the functions of B-cells are impaired, then the concentration of HIV is increased in the plasma. Moreover, we observe that the time delay has a similar effect to drug efficacy. This gives some impression for developing a new class of treatments to increase the delay period and then suppress the HIV replication. [ABSTRACT FROM AUTHOR]

This paper deals with the study of an HIV dynamics model with two target cells, macrophages and CD4 + T cells and three categories of infected cells, short-lived, long-lived and latent in order to get better insights into HIV infection within the body. The model incorporates therapeutic modalities such as reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs). The model is incorporated with distributed time delays to characterize the time between an HIV contact of an uninfected target cell and the creation of mature HIV. The effect of antibody on HIV infection is analyzed. The production and removal rates of the ten compartments of the model are given by general nonlinear functions which satisfy reasonable conditions. Nonnegativity and ultimately boundedness of the solutions are proven. Using the Lyapunov method, the global stability of the equilibria of the model is proven. Numerical simulations of the system are provided to confirm the theoretical results. We have shown that the antibodies can play a significant role in controlling the HIV infection, but it cannot clear the HIV particles from the plasma. Moreover, we have demonstrated that the intracellular time delay plays a similar role as the Highly Active Antiretroviral Therapies (HAAT) drugs in eliminating the HIV particles. [ABSTRACT FROM AUTHOR]

Mathematical models have the potential to contribute to design and evaluate the infectivity spreading and growth of human immunodeficiency virus (HIV). Providing a better understanding of the dynamics of HIV infection in vivo and the immune system interactions with the virus can improve the classification of the infected cells and drive to an early diagnosis of the disease and drug evaluations. We analyze a two-dimensional environment HIV model from a new perspective, in terms of a multi-objective optimization problem, by introducing a linear modeling approach and providing numerical evidence for its suitability by introducing a general Instantaneous Control Algorithm. [ABSTRACT FROM AUTHOR]

Replication of Human Immunodeficiency Virus type 1 (HIV) in infected CD4 + T cells represents a key driver of HIV infection. The HIV life cycle is characterised by the heterogeneity of infected cells with respect to multiplicity of infection and the variability in viral progeny. This heterogeneity can result from the phenotypic diversity of infected cells as well as from random effects and fluctuations in the kinetics of biochemical reactions underlying the virus replication cycle. To quantify the contribution of stochastic effects to the variability of HIV life cycle kinetics, we propose a high-resolution mathematical model formulated as a Markov chain jump process. The model is applied to generate the statistical characteristics of the (i) cell infection multiplicity, (ii) cooperative nature of viral replication, and (iii) variability in virus secretion by phenotypically identical cells. We show that the infection with a fixed number of viruses per CD4 + T cell leads to some heterogeneity of infected cells with respect to the number of integrated proviral genomes. The bottleneck factors in the virus production are identified, including the Gag-Pol proteins. Sensitivity analysis enables ranking of the model parameters with respect to the strength of their impact on the size of viral progeny. The first three globally influential parameters are the transport of genomic mRNA to membrane, the tolerance of transcription activation to Tat-mediated regulation, and the degradation of free and mature virions. These can be considered as potential therapeutical targets. [ABSTRACT FROM AUTHOR]

Complex networks constitute a new field of scientific research that is derived from the observation and analysis of real-world networks, for example, biological, computer and social ones. An important subset of complex networks is the biological, which deals with the numerical examination of connections/associations among different nodes, namely interfaces. These interfaces are evolutionary and physiological, where network epidemic models or even neural networks can be considered as representative examples. The investigation of the corresponding biological networks along with the study of human diseases has resulted in an examination of networks regarding medical supplies. This examination aims at a more profound understanding of concrete networks. Fuzzy logic is considered one of the most powerful mathematical tools for dealing with imprecision, uncertainties and partial truth. It was developed to consider partial truth values, between completely true and completely false, and aims to provide robust and low-cost solutions to real-world problems. In this manuscript, we introduce a fuzzy implementation of epidemic models regarding the Human Immunodeficiency Virus (HIV) spreading in a sample of needle drug individuals. Various fuzzy scenarios for a different number of users and different number of HIV test samples per year are analyzed in order for the samples used in the experiments to vary from case to case. To the best of our knowledge, analyzing HIV spreading with fuzzy-based simulation scenarios is a research topic that has not been particularly investigated in the literature. The simulation results of the considered scenarios demonstrate that the existence of fuzziness plays an important role in the model setup process as well as in analyzing the effects of the disease spread. [ABSTRACT FROM AUTHOR]

Many human virus infections including those with the human immunodeficiency virus type 1 (HIV) are initiated by low numbers of founder viruses. Therefore, random effects have a strong influence on the initial infection dynamics, e.g., extinction versus spread. In this study, we considered the simplest (so-called, 'consensus') virus dynamics model and incorporated a delay between infection of a cell and virus progeny release from the infected cell. We then developed an equivalent stochastic virus dynamics model that accounts for this delay in the description of the random interactions between the model components. The new model is used to study the statistical characteristics of virus and target cell populations. It predicts the probability of infection spread as a function of the number of transmitted viruses. A hybrid algorithm is suggested to compute efficiently the system dynamics in state space domain characterized by the mix of small and large species densities. [ABSTRACT FROM AUTHOR]

We propose a fractional order model to study the efficacy of the Post-Exposure Prophylaxis (PEP) in human immunodeficiency virus (HIV) within-host dynamics, in the presence of the HIV latent reservoir. Latent reservoirs harbor infected cells that contain a transcriptionally silent but reactivatable provirus. The latter constitutes a major difficulty to the eradication of HIV in infected patients. PEP is used as a way to prevent HIV infection after a recent possible exposure to HIV. It consists of the in-take of antiretroviral drugs for, usually, 28 days. In this study, we focus on the dosage and dosage intervals of antiretroviral therapy (ART) during PEP and in the role of the latent reservoir in HIV infected patients. We thus simulate the model for immunologically important parameters concerning the drugs and the fraction of latently infected cells. The results may add important information to clinical practice of HIV infected patients. [ABSTRACT FROM AUTHOR]