14,112 research outputs found
Experimental and computational analyses reveal that environmental restrictions shape HIV-1 spread in 3D cultures
Here, using an integrative experimental and computational approach, Imle et al. show how cell motility and density affect HIV cell-associated transmission in a three-dimensional tissue-like culture system of CD4+ T cells and collagen, and how different collagen matrices restrict infection by cell-free virions
Mathematical modelling of internal HIV dynamics
We study a mathematical model for the viral dynamics of HIV in an infected individual in the presence of HAART. The paper starts with a literature review and then formulates the basic mathematical model. An expression for R0, the basic reproduction number of the virus under steady state application of HAART, is derived followed by an equilibrium and stability analysis. There is always a disease-free equilibrium (DFE) which is globally asymptotically stable for R0 1 then some simulations will die out whereas others will not. Stochastic simulations suggest that if R0 > 1 those which do not die out approach a stochastic quasi-equilibrium consisting of random uctuations about the non-trivial deterministic equilibrium levels, but the amplitude of these uctuations is so small that practically the system is at the non-trivial equilibrium. A brief discussion concludes the paper
Modeling long-term longitudinal HIV dynamics with application to an AIDS clinical study
A virologic marker, the number of HIV RNA copies or viral load, is currently
used to evaluate antiretroviral (ARV) therapies in AIDS clinical trials. This
marker can be used to assess the ARV potency of therapies, but is easily
affected by drug exposures, drug resistance and other factors during the
long-term treatment evaluation process. HIV dynamic studies have significantly
contributed to the understanding of HIV pathogenesis and ARV treatment
strategies. However, the models of these studies are used to quantify
short-term HIV dynamics ( 1 month), and are not applicable to describe
long-term virological response to ARV treatment due to the difficulty of
establishing a relationship of antiviral response with multiple treatment
factors such as drug exposure and drug susceptibility during long-term
treatment. Long-term therapy with ARV agents in HIV-infected patients often
results in failure to suppress the viral load. Pharmacokinetics (PK), drug
resistance and imperfect adherence to prescribed antiviral drugs are important
factors explaining the resurgence of virus. To better understand the factors
responsible for the virological failure, this paper develops the
mechanism-based nonlinear differential equation models for characterizing
long-term viral dynamics with ARV therapy. The models directly incorporate drug
concentration, adherence and drug susceptibility into a function of treatment
efficacy and, hence, fully integrate virologic, PK, drug adherence and
resistance from an AIDS clinical trial into the analysis. A Bayesian nonlinear
mixed-effects modeling approach in conjunction with the rescaled version of
dynamic differential equations is investigated to estimate dynamic parameters
and make inference. In addition, the correlations of baseline factors with
estimated dynamic parameters are explored and some biologically meaningful
correlation results are presented. Further, the estimated dynamic parameters in
patients with virologic success were compared to those in patients with
virologic failure and significantly important findings were summarized. These
results suggest that viral dynamic parameters may play an important role in
understanding HIV pathogenesis, designing new treatment strategies for
long-term care of AIDS patients.Comment: Published in at http://dx.doi.org/10.1214/08-AOAS192 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Global dynamics of cell mediated immunity in viral infection models with distributed delays
In this paper, we investigate global dynamics for a system of delay
differential equations which describes a virus-immune interaction in
\textit{vivo}. The model has two distributed time delays describing time needed
for infection of cell and virus replication. Our model admits three possible
equilibria, an uninfected equilibrium and infected equilibrium with or without
immune response depending on the basic reproduction number for viral infection
and for CTL response such that . It is shown that
there always exists one equilibrium which is globally asymptotically stable by
employing the method of Lyapunov functional. More specifically, the uninfected
equilibrium is globally asymptotically stable if , an infected
equilibrium without immune response is globally asymptotically stable if
and an infected equilibrium with immune response is globally
asymptotically stable if . The immune activation has a positive role
in the reduction of the infection cells and the increasing of the uninfected
cells if .Comment: 16 pages, accepted by Journal of Mathematical Analysis and
Application
Hybrid spreading mechanisms and T cell activation shape the dynamics of HIV-1 infection
HIV-1 can disseminate between susceptible cells by two mechanisms: cell-free
infection following fluid-phase diffusion of virions and by highly-efficient
direct cell-to-cell transmission at immune cell contacts. The contribution of
this hybrid spreading mechanism, which is also a characteristic of some
important computer worm outbreaks, to HIV-1 progression in vivo remains
unknown. Here we present a new mathematical model that explicitly incorporates
the ability of HIV-1 to use hybrid spreading mechanisms and evaluate the
consequences for HIV-1 pathogenenesis. The model captures the major phases of
the HIV-1 infection course of a cohort of treatment naive patients and also
accurately predicts the results of the Short Pulse Anti-Retroviral Therapy at
Seroconversion (SPARTAC) trial. Using this model we find that hybrid spreading
is critical to seed and establish infection, and that cell-to-cell spread and
increased CD4+ T cell activation are important for HIV-1 progression. Notably,
the model predicts that cell-to-cell spread becomes increasingly effective as
infection progresses and thus may present a considerable treatment barrier.
Deriving predictions of various treatments' influence on HIV-1 progression
highlights the importance of earlier intervention and suggests that treatments
effectively targeting cell-to-cell HIV-1 spread can delay progression to AIDS.
This study suggests that hybrid spreading is a fundamental feature of HIV
infection, and provides the mathematical framework incorporating this feature
with which to evaluate future therapeutic strategies
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