A study on the transmission and dynamical behavior of an HIV/AIDS epidemic model with a cure rate

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Abstract

<abstract> In developing nations, the human immunodeficiency virus (HIV) infection, which can lead to acquired immunodeficiency syndrome (AIDS), has become a serious infectious disease. It destroys millions of people and costs incredible amounts of money to treat and control epidemics. In this research, we implemented a Legendre wavelet collocation scheme for the model of HIV infection and compared the new findings to previous findings in the literature. The findings demonstrate the precision and practicality of the suggested approach for approximating the solutions of HIV model. Additionally, establish an autonomous non-linear model for the transmission dynamics of healthy CD4+ T-cells, infected CD4+ T-cells and free particles HIV with a cure rate. Through increased human immunity, the cure rate contributes to a reduction in infected cells and viruses. Using the Routh-Hurwitz criterion, we determine the basic reproductive number and assess the stability of the disease-free equilibrium and unique endemic equilibrium of the model. Furthermore, numerical simulations of the novel model are presented using the suggested approach to demonstrate the efficiency of the key findings. </abstract>

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Transcriptional bursting from the HIV-1 promoter is a significant source of stochastic noise in HIV-1 gene expression.

Abhyudai Singh, Brandon Razooky, Chris D Cox … (2010)

Analysis of noise in gene expression has proven a powerful approach for analyzing gene regulatory architecture. To probe the regulatory mechanisms controlling expression of HIV-1, we analyze noise in gene-expression from HIV-1's long terminal repeat (LTR) promoter at different HIV-1 integration sites across the human genome. Flow cytometry analysis of GFP expression from the HIV-1 LTR shows high variability (noise) at each integration site. Notably, the measured noise levels are inconsistent with constitutive gene expression models. Instead, quantification of expression noise indicates that HIV-1 gene expression occurs through randomly timed bursts of activity from the LTR and that each burst generates an average of 2-10 mRNA transcripts before the promoter returns to an inactive state. These data indicate that transcriptional bursting can generate high variability in HIV-1 early gene products, which may critically influence the viral fate-decision between active replication and proviral latency. Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

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Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy

Ivona Pandrea, Melissa E. Schechter, Bruno B. Andrade … (2017)

In HIV infection, persistent inflammation despite effective antiretroviral therapy is linked to increased risk of noninfectious chronic complications such as cardiovascular and thromboembolic disease. A better understanding of inflammatory and coagulation pathways in HIV infection is needed to optimize clinical care. Markers of monocyte activation and coagulation independently predict morbidity and mortality associated with non-AIDS events. We identified a specific subset of monocytes that express tissue factor (TF), persist after virological suppression, and trigger the coagulation cascade by activating factor X. This subset of monocytes expressing TF had a distinct gene signature with up-regulated innate immune markers and evidence of robust production of multiple proinflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor–α (TNF-α), and IL-6, ex vivo and in vitro upon lipopolysaccharide stimulation. We validated our findings in a nonhuman primate model, showing that TF-expressing inflammatory monocytes were associated with simian immunodeficiency virus (SIV)–related coagulopathy in the progressive [pigtail macaques (PTMs)] but not in the nonpathogenic (African green monkeys) SIV infection model. Last, Ixolaris, an anticoagulant that inhibits the TF pathway, was tested and potently blocked functional TF activity in vitro in HIV and SIV infection without affecting monocyte responses to Toll-like receptor stimulation. Strikingly, in vivo treatment of SIV-infected PTMs with Ixolaris was associated with significant decreases in D-dimer and immune activation. These data suggest that TF-expressing monocytes are at the epicenter of inflammation and coagulation in chronic HIV and SIV infection and may represent a potential therapeutic target.