NDLI: Evaluation of HIV 2-LTR formation models using monotone system theory

Content Provider	IEEE Xplore Digital Library
Author	Piovoso, M.J. Zurakowski, R.
Copyright Year	2014
Description	Author affiliation: Dept. of Electr. & Comput. Eng, Univ. of Delaware, Newark, DE, USA (Zurakowski, R.) \|\| Penn State Univ., University Park, PA, USA (Piovoso, M.J.)
Abstract	An important question in HIV research is whether the combination Antiretroviral Therapy (cART) is capable of fully suppressing the replication of HIV virus. Recent experiments have tested whether this is the case by perturbing the virus dynamics in patients with apparently suppressed HIV replication, as measured by blood viremia levels, by adding an integrase inhibitor raltegravir to the existing cART regimen. Following the addition of raltegravir, a consistent spike followed by decay was observed in the concentrations of a HIV DNA artifact marker, the 2-LTR circle. In previous work, we have shown that a model of ongoing HIV replication explains this behavior, while a model of controlled or absent HIV replication does not. A recent paper by Angeli and Sontag (2012) describes a method of invalidating biological models with sign-definite interactions by considering the monotonicity of the observed outputs relative to the monotonicity of the network description of the model. In this paper, we use this method to evaluate alternative explanations of the observed 2-LTR behavior. We show via monotone system theory that models consistent with the observed non-monotonic response in measured 2-LTR are either biologically infeasible or contain ongoing viral replication.
Starting Page	2747
Ending Page	2752
File Size	1088756
Page Count	6
File Format	PDF
ISBN	9781479932726
ISSN	07431619
e-ISBN	9781479932740
DOI	10.1109/ACC.2014.6858730
Language	English
Publisher	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Publisher Date	2014-06-04
Publisher Place	USA
Access Restriction	Subscribed
Rights Holder	American Automatic Control Council(AACC)
Subject Keyword	Human immunodeficiency virus Mathematical model Biological system modeling Equations DNA Medical treatment Modeling and simulation Biomedical Systems biology
Content Type	Text
Resource Type	Article
Subject	Electrical and Electronic Engineering

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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