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Bioinformatics Advance Access originally published online on October 17, 2007
Bioinformatics 2007 23(24):3350-3355; doi:10.1093/bioinformatics/btm408
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Optimization of HAART with genetic algorithms and agent-based models of HIV infection

F. Castiglione 1,*, F. Pappalardo 2, M. Bernaschi 1 and S. Motta 1

1Institute for Computing Applications ‘M. Picone’, Consiglio Nazionale delle Ricerche (CNR), V.le del Policlinico, 137, 00161 Rome and 2Department of Mathematics and Computer Science, University of Catania, V.le A. Doria 6-I, 95125 Catania Italy

*To whom correspondence should be addressed.


  Abstract

Motivation: Highly Active AntiRetroviral Therapies (HAART) can prolong life significantly to people infected by HIV since, although unable to eradicate the virus, they are quite effective in maintaining control of the infection. However, since HAART have several undesirable side effects, it is considered useful to suspend the therapy according to a suitable schedule of Structured Therapeutic Interruptions (STI).

In the present article we describe an application of genetic algorithms (GA) aimed at finding the optimal schedule for a HAART simulated with an agent-based model (ABM) of the immune system that reproduces the most significant features of the response of an organism to the HIV-1 infection.

Results: The genetic algorithm helps in finding an optimal therapeutic schedule that maximizes immune restoration, minimizes the viral count and, through appropriate interruptions of the therapy, minimizes the dose of drug administered to the simulated patient.

To validate the efficacy of the therapy that the genetic algorithm indicates as optimal, we ran simulations of opportunistic diseases and found that the selected therapy shows the best survival curve among the different simulated control groups.

Availability: A version of the C-IMMSIM simulator is available at http://www.iac.cnr.it/~filippo/c-ImmSim.html

Contact: f.castiglione{at}iac.cnr.it

Associate Editor: Limsoon Wong

Received on May 3, 2007; revised on August 7, 2007; accepted on August 7, 2007

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