Optimization of Interruptions in HIV treatment using a multiscale mechanistic model

Serena Xu, Premanand A. Srinivasan, Antonios Armaou

Research output: Contribution to journalConference article

Abstract

Highly Active Anti-Retroviral Therapy (HAART) regimens are employed to control HIV infection for extended periods of time, but with significant monetary cost and toxic side-effects. To mitigate these difficulties while achieving a similar viral suppression, interruptions in treatment have been explored. In this paper, we use a multiscale model of HIV infection with drug-resistant mutant strains to optimize these treatment interruptions for maximal viral suppression and minimal drug intake. Specifically, a genetic algorithm is used to maximize the duration of viral load below detection limit (<100 virions/mL), while minimizing the average maximal plasma drug concentration (Cmax) for triple-drug HAART regimens with NFV, AZT, and 3TC. Five treatment regimens of increasing complexity are investigated and compared with that of two optimized continuous HAART. The optimized treatment schedules lead to similar viremia-free periods while achieving significant reduction in the amount of drug used.

Original languageEnglish (US)
Article number7039855
Pages (from-to)3029-3034
Number of pages6
JournalProceedings of the IEEE Conference on Decision and Control
Volume2015-February
Issue numberFebruary
DOIs
StatePublished - Jan 1 2014
Event2014 53rd IEEE Annual Conference on Decision and Control, CDC 2014 - Los Angeles, United States
Duration: Dec 15 2014Dec 17 2014

Fingerprint

Multiscale Model
Drugs
Genetic algorithms
Plasmas
Optimization
Therapy
HIV Infection
Costs
Detection Limit
Period of time
Mutant
Schedule
Plasma
Maximise
Optimise
Genetic Algorithm

All Science Journal Classification (ASJC) codes

  • Control and Systems Engineering
  • Modeling and Simulation
  • Control and Optimization

Cite this

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abstract = "Highly Active Anti-Retroviral Therapy (HAART) regimens are employed to control HIV infection for extended periods of time, but with significant monetary cost and toxic side-effects. To mitigate these difficulties while achieving a similar viral suppression, interruptions in treatment have been explored. In this paper, we use a multiscale model of HIV infection with drug-resistant mutant strains to optimize these treatment interruptions for maximal viral suppression and minimal drug intake. Specifically, a genetic algorithm is used to maximize the duration of viral load below detection limit (<100 virions/mL), while minimizing the average maximal plasma drug concentration (Cmax) for triple-drug HAART regimens with NFV, AZT, and 3TC. Five treatment regimens of increasing complexity are investigated and compared with that of two optimized continuous HAART. The optimized treatment schedules lead to similar viremia-free periods while achieving significant reduction in the amount of drug used.",
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Optimization of Interruptions in HIV treatment using a multiscale mechanistic model. / Xu, Serena; Srinivasan, Premanand A.; Armaou, Antonios.

In: Proceedings of the IEEE Conference on Decision and Control, Vol. 2015-February, No. February, 7039855, 01.01.2014, p. 3029-3034.

Research output: Contribution to journalConference article

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AU - Xu, Serena

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AB - Highly Active Anti-Retroviral Therapy (HAART) regimens are employed to control HIV infection for extended periods of time, but with significant monetary cost and toxic side-effects. To mitigate these difficulties while achieving a similar viral suppression, interruptions in treatment have been explored. In this paper, we use a multiscale model of HIV infection with drug-resistant mutant strains to optimize these treatment interruptions for maximal viral suppression and minimal drug intake. Specifically, a genetic algorithm is used to maximize the duration of viral load below detection limit (<100 virions/mL), while minimizing the average maximal plasma drug concentration (Cmax) for triple-drug HAART regimens with NFV, AZT, and 3TC. Five treatment regimens of increasing complexity are investigated and compared with that of two optimized continuous HAART. The optimized treatment schedules lead to similar viremia-free periods while achieving significant reduction in the amount of drug used.

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