Search Results (9)

Acute HIV-1 infection (AHI) is a transient period where the virus causes evident damage to the immune system, including an extensive apoptosis of CD4+ T cells associated with a high level of activation and a major cytokine storm to fight the invading virus. HIV infection establishes persistence by integrating the viral genome into host cell DNA in both replicating and non-replicating forms, effectively hiding from immune surveillance within infected lymphocytes as cellular reservoirs. The measurement of total HIV-1 DNA in peripheral blood mononuclear cells (PBMCs) is a reliable reflection of this reservoir. Initiating treatments during AHI with nucleoside reverse transcriptase inhibitors (NRTIs) and/or integrase strand transfer inhibitors (INSTIs) is essential to alter the dynamics of the global reservoir expansion, and to reduce the establishment of long-lived cellular and tissue reservoirs, while preserving and enhancing specific and non-specific immune responses. Furthermore, some of the patients treated at the AHI stage may become post-treatment controllers and should be informative regarding the mechanism of viral control, so patients treated during AHI are undoubtedly the best candidates to test innovative remission strategies toward a functional cure that could play a pivotal role in long-term HIV control. AHI is characterized by high levels of viral replication, with a significant increase in the risk of HIV transmission. Detecting AHI and initiating early treatment following diagnosis provides a window of opportunity to control the epidemic, particularly in high-risk populations. Full article

Taking into account the effects of the immune response and delay, and complexity on HIV-1 transmission, a multiscale AIDS/HIV-1 model is formulated in this paper. The multiscale model is described by a within-host fast time model with intracellular delay and immune delay, and a between-host slow time model with latency delay. The dynamics of the fast time model is analyzed, and includes the stability of equilibria and properties of Hopf bifurcation. Further, for the coupled slow time model without an immune response, the basic reproduction number ${\mathcal{R}}_0^h$ is defined, which determines whether the model may have zero, one, or two positive equilibria under different conditions. This implies that the slow time model demonstrates more complex dynamic behaviors, including saddle-node bifurcation, backward bifurcation, and Hopf bifurcation. For the other case, that is, the coupled slow time model with an immune response, the threshold dynamics, based on the basic reproduction number ${\tilde{\mathcal{R}}}_0^h$, is rigorously investigated. More specifically, if ${\tilde{\mathcal{R}}}_0^h<1$, the disease-free equilibrium is globally asymptotically stable; if ${\tilde{\mathcal{R}}}_0^h>1$, the model exhibits a unique endemic equilibrium that is globally asymptotically stable. With regard to the coupled slow time model with an immune response and stable periodic solution, the basic reproduction number ${\mathcal{R}}_0$ is derived, which serves as a threshold value determining whether the disease will die out or lead to periodic oscillations in its prevalence. The research results suggest that the disease is more easily controlled when hosts have an extensive immune response and the time required for new immune particles to emerge in response to antigenic stimulation is within a certain range. Finally, numerical simulations are presented to validate the main results and provide some recommendations for controlling the spread of HIV-1. Full article

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. Full article

The global incidence of sexually transmitted infections (STIs) remains high, with the World Health Organization (WHO) estimating that over 1 million people acquire STIs daily. STIs can lead to infertility, pregnancy complications, and cancers. Co-infections with multiple pathogens are prevalent among individuals with an STI and can lead to heightened infectivity and more severe clinical manifestations. Chlamydia trachomatis (CT) is the most reported bacterial STI worldwide in both men and women, and several studies have demonstrated co-infection of CT with viral and other bacterial STIs. CT is a gram-negative bacterium with a unique biphasic developmental cycle including infectious extracellular elementary bodies (EBs) and metabolically active intracellular reticulate bodies (RBs). The intracellular form of this organism, RBs, has evolved mechanisms to persist for long periods within host epithelial cells in a viable but non-cultivable state. The co-infections of CT with the most frequently reported sexually transmitted viruses: human immunodeficiency virus (HIV), human papillomavirus (HPV), and herpes simplex virus (HSV) have been investigated through in vitro and in vivo studies. These research studies have made significant strides in unraveling the intricate interactions between CT, these viral STIs, and their eukaryotic host. In this review, we present an overview of the epidemiology of these co-infections, while specifically delineating the underlying mechanisms by which CT influences the transmission and infection dynamics of HIV and HSV. Furthermore, we explore the intricate relationship between CT and HPV infection, with a particular emphasis on the heightened risk of cervical cancer. By consolidating the current body of knowledge, we provide valuable insights into the complex dynamics and implications of co-infection involving CT and sexually transmitted viruses. Full article

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 ${\Re }_0$ and ${\tilde{\Re }}_0$, 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. Full article

Human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type I (HTLV-I) are two retroviruses which infect the same target, CD$4^{+}$ T cells. This type of cell is considered the main component of the immune system. Since both viruses have the same means of transmission between individuals, HIV-1-infected patients are more exposed to the chance of co-infection with HTLV-I, and vice versa, compared to the general population. The mathematical modeling and analysis of within-host HIV-1/HTLV-I co-infection dynamics can be considered a robust tool to support biological and medical research. In this study, we have formulated and analyzed an HIV-1/HTLV-I co-infection model with humoral immunity, taking into account both latent HIV-1-infected cells and HTLV-I-infected cells. The model considers two modes of HIV-1 dissemination, virus-to-cell (V-T-C) and cell-to-cell (C-T-C). We prove the nonnegativity and boundedness of the solutions of the model. We find all steady states of the model and establish their existence conditions. We utilize Lyapunov functions and LaSalle’s invariance principle to investigate the global stability of all the steady states of the model. Numerical simulations were performed to illustrate the corresponding theoretical results. The effects of humoral immunity and C-T-C transmission on the HIV-1/HTLV-I co-infection dynamics are discussed. We have shown that humoral immunity does not play the role of clearing an HIV-1 infection but it can control HIV-1 infection. Furthermore, we note that the omission of C-T-C transmission from the HIV-1/HTLV-I co-infection model leads to an under-evaluation of the basic HIV-1 mono-infection reproductive ratio. Full article

A mathematical model for the transmission dynamics of human immunodeficiency virus (HIV) within a host is developed. Our model focuses on the roles of immune response cells or cytotoxic lymphocytes (CTLs). The model includes active and inactive cytotoxic immune cells. The basic reproduction number and the global stability of the virus free equilibrium is carried out. The model is modified to include anti-retroviral treatment interventions and the controlled reproduction number is explored. Their effects on the HIV infection dynamics are investigated. Two different disease stage scenarios are assessed: early-stage and advanced-stage of the disease. Furthermore, optimal control theory is employed to enhance healthy CD4${}^{+}$ T cells, active cytotoxic immune cells and minimize the total cost of anti-retroviral treatment interventions. Two different anti-retroviral treatment interventions (RTI and PI) are incorporated. The results highlight the key roles of cytotoxic immune response in the HIV infection dynamics and corresponding optimal treatment strategies. It turns out that the combined control (both RTI and PI) and stronger immune response is the best intervention to maximize healthy CD4${}^{+}$ T cells at a minimal cost of treatments. Full article

Viruses must continuously evolve to hijack the host cell machinery in order to successfully replicate and orchestrate key interactions that support their persistence. The type-1 human immunodeficiency virus (HIV-1) is a prime example of viral persistence within the host, having plagued the human population for decades. In recent years, advances in cellular imaging and molecular biology have aided the elucidation of key steps mediating the HIV-1 lifecycle and viral pathogenesis. Super-resolution imaging techniques such as stimulated emission depletion (STED) and photoactivation and localization microscopy (PALM) have been instrumental in studying viral assembly and release through both cell–cell transmission and cell–free viral transmission. Moreover, powerful methods such as Forster resonance energy transfer (FRET) and bimolecular fluorescence complementation (BiFC) have shed light on the protein-protein interactions HIV-1 engages within the host to hijack the cellular machinery. Specific advancements in live cell imaging in combination with the use of multicolor viral particles have become indispensable to unravelling the dynamic nature of these virus-host interactions. In the current review, we outline novel imaging methods that have been used to study the HIV-1 lifecycle and highlight advancements in the cell culture models developed to enhance our understanding of the HIV-1 lifecycle. Full article

The diversity of HIV-1 and its propensity to generate escape mutants present fundamental challenges to control efforts, including HIV vaccine design. Intra-host diversification of HIV is determined by immune responses elicited by an HIV-infected individual over the course of the infection. Complex and dynamic patterns of transmission of HIV lead to an even more complex population viral diversity over time, thus presenting enormous challenges to vaccine development. To address inter-patient viral evolution over time, a set of 653 unique HIV-1 subtype C gag sequences were retrieved from the LANL HIV Database, grouped by sampling year as <2000, 2000, 2001–2002, 2003, and 2004–2006, and analyzed for the site-specific frequency of translated amino acid residues. Phylogenetic analysis revealed that a total of 289 out of 653 (44.3%) analyzed sequences were found within 16 clusters defined by aLRT of more than 0.90. Median (IQR) inter-sample diversity of analyzed gag sequences was 8.7% (7.7%; 9.8%). Despite the heterogeneous origins of analyzed sequences, the gamut and frequency of amino acid residues in wild-type Gag were remarkably stable over the last decade of the HIV-1 subtype C epidemic. The vast majority of amino acid residues demonstrated minor frequency fluctuation over time, consistent with the conservative nature of the HIV-1 Gag protein. Only 4.0% (20 out of 500; HXB2 numbering) amino acid residues across Gag displayed both statistically significant (p<0.05 by both a trend test and heterogeneity test) changes in amino acid frequency over time as well as a range of at least 10% in the frequency of the major amino acid. A total of 59.2% of amino acid residues with changing frequency of 10%+ were found within previously identified CTL epitopes. The time of the most recent common ancestor of the HIV-1 subtype C was dated to around 1950 (95% HPD from 1928 to 1962). This study provides evidence for the overall stability of HIV-1 subtype C Gag among viruses circulating in the epidemic over the last decade. However selected sites across HIV-1C Gag with changing amino acid frequency are likely to be under selection pressure at the population level. Full article