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In this paper, we study a model that enhances our understanding of cytokine-influenced HIV-1 infection. The impact of adaptive immune response (cytotoxic T lymphocytes (CTLs) and antibodies) and time delay on HIV-1 infection is included. The model takes into account two types of distributional delays, (i) the delay in the HIV-1 infection of CD4+T cells and (ii) the maturation delay of new virions. We first investigated the fundamental characteristics of the system, then found the system's equilibria. We derived five threshold parameters, ℜ i , i = 0, 1,..., 4, which completely determine the existence and stability of the equilibria. The Lyapunov method was used to prove the global asymptotic stability for all equilibria. We illustrate the theoretical results by performing numerical simulations. We also performed a sensitivity analysis on the basic reproduction number ℜ 0 and identified the most-sensitive parameters. We found that pyroptosis contributes to the number ℜ 0 , and then, neglecting it will make ℜ 0 underevaluated. Necrosulfonamide and highly active antiretroviral drug therapy (HAART) can be effective in preventing pyroptosis and at reducing viral replication. Further, it was also found that increasing time delays can effectively decrease ℜ 0 and, then, inhibit HIV-1 replication. Furthermore, it is shown that both CTLs and antibody immune responses have no effect on ℜ 0 , while this can result in less HIV-1 infection. [ABSTRACT FROM AUTHOR]

In this paper, the dynamical behaviors of a multiple delayed HIV-1 infection model which describes the interactions of humoral, cytotoxic T lymphocyte (CTL) immune responses, and two modes of transmission that are the classical virus-to-cell infection and the direct cell-to-cell transmission are investigated. The model incorporates three delays, including the delays of cell infection, virus production and activation of immune response. We first prove the well-posedness of the model, and calculate the biological existence of equilibria and the reproduction numbers, which contain virus infection, humoral immune response, CTL immune response, CTL immune competition, and humoral immune competition. Further, the threshold conditions for the local and global stability of the equilibria for infection-free, immune-free, antibody response, CTL response, and interior are established by utilizing linearization method and the Lyapunov functionals. The existence of Hopf bifurcation with immune delay as a bifurcation parameter is investigated by using the bifurcation theory. Numerical simulations are carried out to illustrate the theoretical results and reveal the effects of some key parameters on viral dynamics. [ABSTRACT FROM AUTHOR]

The time fractional-order nonlinear model of HIV-1 infection of T-cells with and without the rate of virus-producing cells’ death is very important in mathematical modeling. This paper presents proofs of the existence and uniqueness theorems using the Banach fixed point theorem, along with new approximate analytical solutions to two nonlinear fractional Equationuations characterizing HIV-1 infection in $CD{4^ + }$CD4+ T-cells. We use a combination of two methods, namely the natural transform method to deal with the linear terms and the Adomian decomposition method to deal with the nonlinear terms. There are two nonlinear numerical examples presented in this work, namely, we find approximate solutions to the time fractional-order nonlinear model of HIV-1 infection of T cells with and without the rate of virus-producing cells’ death using an effective method called the Adomian natural decomposition method (ANDM). The present approach, which has numerous applications in the science and engineering fields, is a great alternative to the many existing methods for solving systems of differential Equationuations. It also holds great promise for additional real-world applications. The Mathematica 12 package is used to carry out some of the nonlinear term calculations and the graphs presented in this work. [ABSTRACT FROM AUTHOR]

It is well known that dynamical systems are very useful tools to study viral diseases such as HIV, HBV, HCV, Ebola and Influenza. This paper focuses on a mathematical model of the cell-to-cell and the cell-free spread of HIV with both linear and nonlinear functional responses and logistic target cell growth. The reproduction number of each mode of transmission has been calculated and their sum has been considered as the basic reproduction number. Based on the values of the reproduction number, the local and global stabilities of the rest points are investigated. Choosing a suitable bifurcation parameter, some conditions for the occurrence of Hopf bifurcation are also obtained. Moreover, numerical simulations are presented to support the analytical results. Finally, to study the effect of the drug on the disease process, some control conditions are determined. Since two modes of transmission and both linear and nonlinear functional responses have been included in this manuscript, our obtained results are a generalization of those in the literature. Moreover, the results are obtained with weaker assumptions in comparison with the previous ones. [ABSTRACT FROM AUTHOR]

In this paper, we incorporate immune systems containing Cytotoxic T lymphocyte and humoral immunity into a general human immunodeficiency viruses infection model, which also considers logistic growth for target cells and both modes of spread, cell-to-cell and cell-free represents, by linear functions. We derive five threshold parameters which are used to study the existence of equilibria. By considering the characteristic equations, the local stability of disease-free and immune-free equilibria is investigated. Lyapunov functions and LaSalle's invariance are constructed to prove the global stability of all steady states. Global dynamics of the human immunodeficiency viruses model can be accurately expressed by threshold parameters; also the existence of Hopf bifurcation is discussed and the results are expressed in the form of a proposition. Furthermore, numerical simulations confirm the corresponding theoretical results. [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]

The two-drug regimen dolutegravir plus lamivudine demonstrated durable efficacy for up to 3 years in phase III studies and a high barrier to resistance in treatment-naive and virologically suppressed people with HIV (PWH). This systematic literature review summarizes real-world evidence evaluating effectiveness and safety of dolutegravir plus lamivudine. We searched Ovid MEDLINE®, Embase®, PubMed, Cochrane library, and relevant international conference proceedings from 2013 to 2020. Qualitative synthesis of virologic suppression at Week 48, treatment-emergent resistance, discontinuation rates, and comorbidities was undertaken, with no statistical analyses conducted. Linked publications and potential for duplication in reporting of outcomes for cohorts and populations were identified, and the publication reporting the highest number of PWH receiving dolutegravir plus lamivudine was included in the analysis. Thirty-four studies reporting on cohorts of PWH not suspected to be linked or to include duplicate data receiving dolutegravir plus lamivudine were identified (N = 5017). Of 3744 virologically suppressed PWH who switched to dolutegravir plus lamivudine, 603 (16%) reported history of virologic failure. Nineteen studies included effectiveness data (n = 3558), four of which included data from treatment-naive PWH (n = 69). In studies with > 100 PWH, high rates of virologic suppression (Week 48, 97–100%) were maintained with dolutegravir plus lamivudine, with low rates of virologic failure (0–3.3 per 100 person-years of follow-up); one instance of emergent integrase strand transfer inhibitor resistance was reported in a complex treatment-experienced individual. Rates of discontinuation due to adverse events were low and consistent with previously observed trial data. Dolutegravir plus lamivudine minimally impacted renal function and had minimal impact on or improved lipid profiles and bone mineral density. This systematic review demonstrates that effectiveness and safety of dolutegravir plus lamivudine in clinical practice support data from randomized controlled trials with regard to high rates of virologic response, low rates of discontinuation, and a high barrier to resistance. [ABSTRACT FROM AUTHOR]

The paper is focused on stochastic modelling of the process of transition of infected cells and virions of HIV-1 infection between two lymph nodes. The model is based on the following assumptions: (1) the duration of transition of infected cells and virions between two lymph nodes is set using a time-dependent function, (2) infected cells produce virions in the process of transition between two lymph nodes, (3) infected cells and virions may die when moving between two lymph nodes. The methods of the theory of branching random processes are used to study analytically the model variables. An algorithm for statistical modelling of the number of infected cells and virions in the second lymph node is presented. The results of computational experiments studying the distribution law of the number of virions produced by one infected cell depending on the duration of movement between two lymph nodes are presented. [ABSTRACT FROM AUTHOR]

In this paper, we investigate an in-host model for the viral dynamics of HIV-1 infection and its interaction with the CTL immune response. The model is sufficiently general to allow nonlinear forms for both viral infection and CTL response. Threshold parameters are identified that completely determine the global dynamics and outcomes of the virus-target cell-CTL interactions. Impacts of key parameter values for CTL functions and viral budding rate on the HIV-1 viral load and CD4 count are investigated using numerical simulations. Results support clinical evidence for important differences between HIV-1 nonprogressors and progressors. [ABSTRACT FROM AUTHOR]

In this paper, we propose and analyse a delayed HIV-1 model with both viral and cellular transmissions and virus waning. We obtain the threshold dynamics of the proposed model, characterized by the basic reproduction number R 0 . If R 0 < 1 , the infection-free steady state is globally asymptotically stable; whereas if R 0 > 1 , the system is uniformly persistent. When the delays are positive, we show that the intracellular delays in both viral and cellular infections may lead to stability switches of the infected steady state. Both analytical and numerical results indicate that if the effect of cell-to-cell transmission is ignored, then the risk of HIV-1 infection will be underestimated. Moreover, the viral load of model without virus waning is higher than the one of model with virus waning. These results highlight the important role of two ways of viral transmission and virus waning on HIV-1 infection. [ABSTRACT FROM AUTHOR]

Summary: In this paper, we consider a four‐dimensional version of a human immunodeficiency virus (HIV) infection model, which is an extension of some previous three‐dimensional models. We approach the treatment problem by adding two controls u1 and u2 to the system for inhibiting viral production and preventing new infections. In fact, u1 is added to components of uninfected and infected cells to represent the effect of chemotherapy on the interaction of uninfected CD4+ T cells with infected cells. u2 is considered in the effector immune component as immunotherapy. The purpose of this work is to control the progress of the disease in a steady state. Hence, first, we obtain a relation between the two controls u1 and u2 such that a Hopf bifurcation occurs. Next, the Pontryagin minimum principle will be applied to derive the optimal therapy for HIV. At the end, numerical results are presented. [ABSTRACT FROM AUTHOR]

HIV-associated neurocognitive disorders (HAND) persist under antiretroviral therapy as a complex pathology that has been difficult to study in cellular and animal models. Therefore, we generated an ex vivo human brain slice model of HIV-1 infection from surgically resected adult brain tissue. Brain slice cultures processed for flow cytometry showed >90% viability of dissociated cells within the first three weeks in vitro, with parallel detection of astrocyte, myeloid, and neuronal populations. Neurons within brain slices showed stable dendritic spine density and mature spine morphologies in the first weeks in culture, and they generated detectable activity in multi-electrode arrays. We infected cultured brain slices using patient-matched CD4+ T-cells or monocyte-derived macrophages (MDMs) that were exposed to a GFP-expressing R5-tropic HIV-1 in vitro. Infected slice cultures expressed viral RNA and developed a spreading infection up to 9 days post-infection, which were significantly decreased by antiretrovirals. We also detected infected myeloid cells and astrocytes within slices and observed minimal effect on cellular viability over time. Overall, this human-centered model offers a promising resource to study the cellular mechanisms contributing to HAND (including antiretroviral toxicity, substance use, and aging), infection of resident brain cells, and new neuroprotective therapeutics. [ABSTRACT FROM AUTHOR]

The modern antiretroviral treatment of human immunodeficiency virus (HIV-1) infection has considerably lowered the incidence of opportunistic infections. With the exception of the most severe dementia manifestations, the incidence and prevalence of HIV-associated neurocognitive disorders (HAND) have not decreased, and HAND continues to be relevant in daily clinical practice. Now, HAND occurs in earlier stages of HIV infection, and the clinical course differs from that before the widespread use of combination antiretroviral treatment (cART). The predominant clinical feature is a subcortical dementia with deficits in the domains concentration, attention, and memory. Motor signs such as gait disturbance and impaired manual dexterity have become less prominent. Prior to the advent of cART, the cerebral dysfunction could at least partially be explained by the viral load and by virus-associated histopathological findings. In subjects where cART has led to undetectable or at least very low viral load, the pathogenic virus-brain interaction is less direct, and an array of poorly understood immunological and probably toxic phenomena are discussed. This paper gives an overview of the current concepts in the field of HAND and provides suggestions for the diagnostic and therapeutic management. [ABSTRACT FROM AUTHOR]

In this paper, we consider a four dimensional model of the human immunodeficiency virus-1 (HIV-1) with delay, which is an extension of some three dimensional models. We approach the treatment problem by adding two controllers to the system for inhibiting viral production. The optimal controller $$u_{1}$$ is considered for vaccine and $$u_{2}$$ for the drug. The Pontryagin maximum principle with delay is used to characterize these optimal controls. At the end, numerical results are presented to illustrate the optimal solutions. The validity of the model was confirmed by proper semi-quantitative simulation of some clinical data. The model was used to predict the possible beneficial effects of vaccine and anti-retroviral drug administration in HIV-1 disease. [ABSTRACT FROM AUTHOR]

HIV infection is one of the most serious causes of death throughout the world. CD4+ T cells which play an important role in immune protection, are the primary targets for HIV infection. The hallmark of HIV infection is the progressive loss in population of CD4+ T cells. However, the pathway causing this slow T cell decline is poorly understood [16]. This paper studies a discontinuous mathematical model for HIV-1 infection, to investigate the effect of pyroptosis on the disease. For this purpose, we use the theory of discontinuous dynamical systems. In this way, we can better analyze the dynamical behavior of the HIV-1 system. Especially, considering the dynamics of the system on its discontinuity boundary enables us to obtain more comprehensive results rather than the previous researches. A stability region for the system, corresponding to its equilibria on the discontinuity boundary, will be determined. In such a parametric region, the trajectories of the system will be trapped on the discontinuity manifold forever. It is also shown that in the obtained stability region, the disease can lead to a steady state in which the population of uninfected T cells and viruses will preserve at a constant level of cytokines. This means that the pyroptosis will be restricted and the disease cannot progress for a long time. Some numerical simulations based on clinical and experimental data are given which are in good agreement with our theoretical results. [ABSTRACT FROM AUTHOR]

In this paper, an attempt has been made to study the global dynamical behavior of a viral dynamics model incorporating both the lytic and nonlytic immune responses. The global stability of the model is analyzed in terms of two threshold parameters, namely, basic reproduction number, R 0 and immune response reproduction number, R 1. The obtained results signify that the infection dies out if R 0 ≤ 1 and persists if R 0 > 1. We establish that the global dynamic behavior of the model has no concern with the efficacy of the nonlytic component. Numerical simulations are performed to support our theoretical findings and to investigate the effects of lytic and nonlytic components on the viral dynamics model. A comparison of two different viral infection models has been performed to illustrate the effect of viral replication inhibition through nonlytic effector mechanism on the infection dynamics. Moreover, a case study of HIV-1 infected humanized mice is presented and the result manifests that the model can fairly demonstrate the chronic stage of HIV-1 infection in humanized mice. • A viral dynamic model with lytic and nonlytic immune responses has been presented. • Global stability of the model is independent of the efficacy of nonlytic strength. • Inhibition of viral replication reduces the level of infected cells and virions. • The model fairly demonstrates the chronic HIV-1 infection in humanized mice. [ABSTRACT FROM AUTHOR]

HIV-1 has evolved a plethora of strategies to overcome the cytoskeletal barrier (i.e., actin and intermediate filaments (AFs and IFs) and microtubules (MTs)) to achieve the viral cycle. HIV-1 modifies cytoskeletal organization and dynamics by acting on associated adaptors and molecular motors to productively fuse, enter, and infect cells and then traffic to the cell surface, where virions assemble and are released to spread infection. The HIV-1 envelope (Env) initiates the cycle by binding to and signaling through its main cell surface receptors (CD4/CCR5/CXCR4) to shape the cytoskeleton for fusion pore formation, which permits viral core entry. Then, the HIV-1 capsid is transported to the nucleus associated with cytoskeleton tracks under the control of specific adaptors/molecular motors, as well as HIV-1 accessory proteins. Furthermore, HIV-1 drives the late stages of the viral cycle by regulating cytoskeleton dynamics to assure viral Pr55Gag expression and transport to the cell surface, where it assembles and buds to mature infectious virions. In this review, we therefore analyze how HIV-1 generates a cell-permissive state to infection by regulating the cytoskeleton and associated factors. Likewise, we discuss the relevance of this knowledge to understand HIV-1 infection and pathogenesis in patients and to develop therapeutic strategies to battle HIV-1. [ABSTRACT FROM AUTHOR]

This paper study the dynamical behavior of a general HIV-1 infection model under the effect of Highly active antiretroviral therapies (HAART). The model includes three types of infected cells (i) long-lived productively infected cells which live for long time and creat small amount of HIV-1 particles, (ii) latently infected cells which do not creat HIV-1 until they have been activated (iii) short-lived productively infected cells which live for long time and creat large amount of HIV-1. The model incorporates humoral immune response and general nonlinear forms for the incidence rate of infection, the generation and removal rates of all compartments. The nonnegativity and boundedness of the solutions of the model as well as global stability of the steady states are studied. The global stability are established using Lyapunov method. Using MATLAB we conduct some numerical simulations to confirm our results. [ABSTRACT FROM AUTHOR]

In this research work, we suggest two mathematical models that take into account (i) two categories of target cells, CD 4 + T cells and macrophages, and (ii) two modes of infection transmissions, the direct virus-to-cell (VTC) method and cell-to-cell (CTC) infection transmission, where CTC is an effective method of spreading human immunodeficiency virus type-1 (HIV-1), as with the VTC method. The second model incorporates four time delays. In both models, the presence of a bounded and positive solution of the biological model is investigated. The existence conditions of all equilibria are established. The basic reproduction number R 0 that identifies a disease index is obtained. Lyapunov functions are utilized to verify the global stability of all equilibria. The theoretical findings are verified through numerical simulations. According to the outcomes, the trajectories of the solutions approach the infection-free equilibrium and infection-present equilibrium when R 0 ≤ 1 and R 0 > 1 , respectively. Further, we study the sensitivity analysis to investigate how the values of all the parameters of the suggested model affect R 0 for given data. We discuss the impact of the time delay on HIV-1 progression. We find that a longer time delay results in suppression of the HIV-1 infection and vice versa. [ABSTRACT FROM AUTHOR]

The chemokine receptor CXCR4 and its ligand CXCL12 regulate leukocyte trafficking, homeostasis and functions and are potential therapeutic targets in many diseases such as HIV-1 infection and cancers. Here, we identified new CXCR4 ligands in the CERMN chemical library using a FRET-based high-throughput screening assay. These are bis-imidazoline compounds comprising two imidazole rings linked by an alkyl chain. The molecules displace CXCL12 binding with submicromolar potencies, similarly to AMD3100, the only marketed CXCR4 ligand. They also inhibit anti-CXCR4 mAb 12G5 binding, CXCL12-mediated chemotaxis and HIV-1 infection. Further studies with newly synthesized derivatives pointed out to a role of alkyl chain length on the bis-imidazoline properties, with molecules with an even number of carbons equal to 8, 10 or 12 being the most potent. Interestingly, these differ in the functions of CXCR4 that they influence. Site-directed mutagenesis and molecular docking predict that the alkyl chain folds in such a way that the two imidazole groups become lodged in the transmembrane binding cavity of CXCR4. Results also suggest that the alkyl chain length influences how the imidazole rings positions in the cavity. These results may provide a basis for the design of new CXCR4 antagonists targeting specific functions of the receptor. [ABSTRACT FROM AUTHOR]

In this paper, we study a model that enhances our understanding of cytokine-influenced HIV-1 infection. The impact of adaptive immune response (cytotoxic T lymphocytes (CTLs) and antibodies) and time delay on HIV-1 infection is included. The model takes into account two types of distributional delays, (i) the delay in the HIV-1 infection of CD4+T cells and (ii) the maturation delay of new virions. We first investigated the fundamental characteristics of the system, then found the system’s equilibria. We derived five threshold parameters, ℜi, i = 0, 1,…, 4, which completely determine the existence and stability of the equilibria. The Lyapunov method was used to prove the global asymptotic stability for all equilibria. We illustrate the theoretical results by performing numerical simulations. We also performed a sensitivity analysis on the basic reproduction number ℜ0 and identified the most-sensitive parameters. We found that pyroptosis contributes to the number ℜ0, and then, neglecting it will make ℜ0 underevaluated. Necrosulfonamide and highly active antiretroviral drug therapy (HAART) can be effective in preventing pyroptosis and at reducing viral replication. Further, it was also found that increasing time delays can effectively decrease ℜ0 and, then, inhibit HIV-1 replication. Furthermore, it is shown that both CTLs and antibody immune responses have no effect on ℜ0, while this can result in less HIV-1 infection.

A mathematical model is presented that describes the dynamics of the population of CD4 T-lymphocytes in a single lymph node. The model is based on a high-dimensional system of nonlinear delay differential equations supplemented with initial data. The equations of the model are given, and their well-posedness is investigated. The results of computational experiments with the model illustrating the characteristic cell population dynamics under the conditions of antigen-specific stimulation of the cell reproduction process for cells of various types are presented. [ABSTRACT FROM AUTHOR]

RNA plays an important role in biology, and more than 170 RNA modifications have been identified so far. Post-transcriptional modification of RNA in cells plays a crucial role in the regulation of its stability, transport, processing, and gene expression. So far, the research on RNA modification and the exact role of its enzymes is becoming more and more comprehensive. Human immunodeficiency virus 1 (HIV-1) is an RNA virus and the causative agent of acquired immunodeficiency syndrome (AIDS), which is one of the most devastating viral pandemics in history. More and more studies have shown that HIV has RNA modifications and regulation of its gene expression during infection and replication. This review focuses on several RNA modifications and their regulatory roles as well as the roles that different RNA modifications play during HIV-1 infection, in order to find new approaches for the development of anti-HIV-1 therapeutics. [ABSTRACT FROM AUTHOR]

The transactive response DNA-binding protein (TARDBP/TDP-43) influences the processing of diverse transcripts, including that of histone deacetylase 6 (HDAC6). Here, we assessed TDP-43 activity in terms of regulating CD4+ T-cell permissivity to HIV-1 infection. We observed that overexpression of wt-TDP-43 increased both mRNA and protein levels of HDAC6, resulting in impaired HIV-1 infection independently of the viral envelope glycoprotein complex (Env) tropism. Consistently, using an HIV-1 Env-mediated cell-to-cell fusion model, the overexpression of TDP-43 levels negatively affected viral Env fusion capacity. Silencing of endogenous TDP-43 significantly decreased HDAC6 levels and increased the fusogenic and infection activities of the HIV-1 Env. Using pseudovirus bearing primary viral Envs from HIV-1 individuals, overexpression of wt-TDP-43 strongly reduced the infection activity of Envs from viremic non-progressors (VNP) and rapid progressors (RP) patients down to the levels of the inefficient HIV-1 Envs observed in long-term non-progressor elite controllers (LTNP-EC). On the contrary, silencing endogenous TDP-43 significantly favored the infectivity of primary Envs from VNP and RP individuals, and notably increased the infection of those from LTNP-EC. Taken together, our results indicate that TDP-43 shapes cell permissivity to HIV-1 infection, affecting viral Env fusion and infection capacities by altering the HDAC6 levels and associated tubulin-deacetylase anti-HIV-1 activity. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of the study was to assess hepcidin levels and iron metabolism in otherwise healthy human immunodeficiency virus-1 (HIV-1)-infected males and the influence of antiretroviral therapy on hepcidin production, as data in this group are scarce. Methods: A total of 89 HIV-1-infected males, 42 on effective antiretroviral therapy (ART)—group A, 47 treatment-naïve—group B, and 27 healthy controls—group C, were enrolled. Erythrocytes parameters, iron metabolism parameters, hepcidin, highly sensitive C-reactive protein (hsCRP), interleukin 6 (IL-6), and soluble transferrin receptor (sTfR) levels were assessed. Conditions related to inflammatory activity, systemic metabolic diseases and iron supplementation were exclusion criteria. Convenience sampling was used. Results: Median age in HIV-1 group was 33 years, and 27 years in the control group. Median CD4+ T-cell count was 724 cells/μl in group A, and 488 cells/μl in group B (p = 0.0000). Nadir CD4+ T-cell count was 397 cells/μl in group A and 475 cells/μl in group B (p = 0.0001). Median value of HIV-1 viral load (VL) in group B was 16 900 copies/mL. The hepcidin value was lower in group A than in groups B (p = 0.0008) or C (p = 0.0004), without differences between groups B and C. The hepcidin value correlated with ferritin in groups A (r2 = 0.16; p = 0.008) and B (r2 = 0.39; p = 0.000), but not in group C (r2 = 0.11; p = 0.09). In group A, the hepcidin value correlated with current CD4+ count (r = 0.48, p = 0.0012), but there was no correlation in group B. There were no correlations of hepcidin values with CD4+ T cell nadir in group A (p = 0.371) or in group B (p = 0.477); ART period (p = 0.614); VL in group B (p = 0.71). No abnormalities of iron metabolism, hsCRP, IL-6, or sTfR were noted. Conclusions: Asymptomatic HIV-1 infection does not cause clinically important iron metabolism alterations or increased hepcidin production. Hepcidin values decrease on effective antiretroviral therapy. [ABSTRACT FROM AUTHOR]

In this paper, we propose and analyse a delayed HIV-1 model with both viral and cellular transmissions and virus waning. We obtain the threshold dynamics of the proposed model, characterized by the basic reproduction number $R_0 $. If $R_0 \lt 1 $, the infection-free steady state is globally asymptotically stable; whereas if $R_0 \gt 1 $, the system is uniformly persistent. When the delays are positive, we show that the intracellular delays in both viral and cellular infections may lead to stability switches of the infected steady state. Both analytical and numerical results indicate that if the effect of cell-to-cell transmission is ignored, then the risk of HIV-1 infection will be underestimated. Moreover, the viral load of model without virus waning is higher than the one of model with virus waning. These results highlight the important role of two ways of viral transmission and virus waning on HIV-1 infection.

Purpose of Review: A large amount of data now exists on the virus-specific immune response associated with spontaneous or induced immunologic control of lentiviruses. This review focuses on how the current understanding of HIV-specific immunity might be leveraged into induction of immunologic control and what further research is needed to accomplish this goal. Recent Findings: During chronic infection, the function most robustly associated with immunologic control of HIV-1 is CD8+ T cell cytotoxic capacity. This function has proven difficult to restore in HIV-specific CD8+ T cells of chronically infected progressors in vitro and in vivo. However, progress has been made in inducing an effective CD8+ T cell response prior to lentiviral infection in the macaque model and during acute lentiviral infection in non-human primates. Summary: Further study will likely accelerate the ability to induce an effective CD8+ T cell response as part of prophylactic or therapeutic strategies. [ABSTRACT FROM AUTHOR]

In this paper, we investigate a delayed HIV-1 infection model with immune response. Though a logistic growth is incorporated in the growth of the target cells, our focus is on the effect of delays on the infection dynamics. We first study the existence of steady states, which depends on the basic reproduction number $R_0$. When $R_0\le 1$, there is only the infection-free steady state, which is globally asymptotically stable if $R_0 < 1$. When $R_0> 1$, besides the unstable infection-free steady state, there is a unique infected steady state. We then study the local stability of the infected steady state and local Hopf bifurcation at it. The theoretical analysis indicates that the dynamics scenario is complicated. For example, there can be three sequences of critical values, stability switches and double Hopf bifurcation can occur. Some of the theoretical results are also illustrated with numerical simulations.

Human specific immunity consists of two branches: humoral immunity and cellular immunity. To protect us from pathogens, cell-mediated and humoral immune responses work together to provide the strongest degree of efficacy. In this paper, we propose an HIV-1 model with cell-mediated and humoral immune responses, in which both virus-to-cell infection and cell-to-cell transmission are considered. Five reproduction ratios, namely, immunity-inactivated reproduction ratio, cell-mediated immunity-activated reproduction ratio, humoral immunity-activated reproduction ratio, cell-mediated immunity-competed reproduction ratio and humoral immunity-competed reproduction ratio, are calculated and verified to be sharp thresholds determining the local and global properties of the virus model. Numerical simulations are carried out to illustrate the corresponding theoretical results and reveal the effects of some key parameters on viral dynamics.

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 CD4+ 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.

HIV-1 employs a rich arsenal of viral factors throughout its life cycle and co-opts intracellular trafficking pathways. This exquisitely coordinated process requires precise manipulation of the host microenvironment, most often within defined subcellular compartments. The virus capitalizes on the host by modulating cell-surface proteins and cleverly exploiting nuclear import pathways for post entry events, among other key processes. Successful virus–cell interactions are indeed crucial in determining the extent of infection. By evolving defenses against host restriction factors, while simultaneously exploiting host dependency factors, the life cycle of HIV-1 presents a fascinating montage of an ongoing host–virus arms race. Herein, we provide an overview of how HIV-1 exploits native functions of the host cell and discuss recent findings that fundamentally change our understanding of the post-entry replication events. [ABSTRACT FROM AUTHOR]

Over the past decade, a series of observations linking α4β7, the principal gut‐homing integrin, with various aspects of HIV‐1 infection have generated considerable interest in the field of HIV‐1 research. After the initial report that the major HIV‐1 envelope glycoprotein, gp120, can bind to α4β7, intensive research efforts have been focused on the role of α4β7 as a key factor in HIV‐1 pathogenesis and as a potential target for prevention and treatment. The interaction between α4β7 and its natural ligand, MAdCAM‐1, directs infected CD4+ T cells and HIV‐1 virions carrying incorporated α4β7 to the gut mucosa, which may facilitate HIV‐1 seeding and replication in the intestinal compartment during the early stages of infection. In addition, cells that express high levels of α4β7, such as Th17 cells, represent preferential targets for infection, and their frequency in the circulation was shown to correlate with susceptibility to HIV‐1 infection and disease progression. A number of in vivo studies in nonhuman primates have investigated whether blockage of α4β7 may affect SIV transmission and pathogenesis. Administration of a primatized anti‐α4β7 antibody that blocks MAdCAM‐1 binding to α4β7 was reported to reduce SIV mucosal transmission in rhesus macaques. However, the mechanism responsible for such a protective effect is still undefined, and conflicting results have been reported on the effects of the same antibody, in combination with ART, during the early chronic phase of SIV infection. Thus, despite a series of tantalizing results accrued over the past decade, the jury is still out on the role of α4β7 in HIV‐1 infection. [ABSTRACT FROM AUTHOR]

We consider a mathematical model that describes a viral infection of HIV-1 with both virus-tocell and cell-to-cell transmission, CTL response immune and four distributed delays, describing intracellular delays and immune response delay. One of the main features of the model is that it includes a constant production rate of CTLs export from thymus, and an immune response delay. We derive the basic reproduction number and show that if the basic reproduction number is less than one, then the infection free equilibrium is globally asymptotically stable; whereas, if the basic reproduction number is greater than one, then there exist a chronic infection equilibrium, which is globally asymptotically stable in absence of immune response delay. Furthermore, for the special case with only immune response delay, we determine some conditions for stability switches of the chronic infection equilibrium. Numerical simulations indicate that the intracellular delays and immune response delay can stabilize and/or destabilize the chronic infection equilibrium. [ABSTRACT FROM AUTHOR]