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dc.contributor.author
Oña, Leonardo
dc.contributor.author
Kouyos, Roger D.
dc.contributor.author
Lachmann, Michael
dc.contributor.author
Bonhoeffer, Sebastian
dc.date.accessioned
2019-05-16T09:44:02Z
dc.date.available
2017-06-10T19:37:21Z
dc.date.available
2019-05-16T09:44:02Z
dc.date.issued
2013-07-11
dc.identifier.issn
1742-4682
dc.identifier.other
10.1186/1742-4682-10-44
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/69928
dc.identifier.doi
10.3929/ethz-b-000069928
dc.description.abstract
Background The application of highly active antiretroviral therapy (HAART) against HIV can reduce and maintain viral load below detection limit in many patients. Continuous HAART, however, can have severe side effects. In this context, structured treatment interruptions (STI) were considered to be a promising strategy. However, using CD4 cell count to guide intermittent therapy starting and stopping points, the SMART study (strategies for management of antiretroviral therapy), revealed that STI were associated with increased risk of AIDS and other complications. Additionally, short-term periodic (e.g. one week on / one week off) interruption therapies have shown virus rebound exceeding a given “failure threshold”, without any evidence for the evolution of drug resistance. Currently, the only hypothesis explaining the failure of STI is the “resonance hypothesis”, which posits that treatment failure is due to a resonance effect between the drug treatment and the viral population. In the present study we used a mathematical model to analyse the parameters affecting the output of drug treatment interruption and the premises of the resonance hypothesis. Methods We used a population dynamic model of HIV infection. Simulations and analytical approximations of deterministic and stochastic versions of the model were studied. Results and Conclusion The present study examines the roles of the most important parameters affecting the viral rebound, responsible for drug failure. We related these findings to the resonance hypothesis, and showed that the degree of sustainability of damping oscillations present in the model after the acute phase is strongly linked to their amplitude, which determines the resonance level. Stochastic simulations of the same model even revealed sustained oscillations in virus population for small virus population sizes. Given that pronounced viral load oscillations have not been observed in HIV-1 patients, the link between oscillations and resonance level suggests that treatment failure due to a resonance effect is not plausible. Moreover, the failure threshold is attained before the virus population crosses the set point while growing. As the maximum virus population is reached even after the set point is crossed, the role of resonance effects in the context of treatment interruptions cannot explain drug failure.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
BioMed Central
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/2.0/
dc.title
On the role of resonance in drug failure under HIV treatment interruption
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 2.0 Generic
ethz.journal.title
Theoretical Biology and Medical Modelling
ethz.journal.volume
10
en_US
ethz.journal.issue
1
en_US
ethz.journal.abbreviated
Theor. biol. med. model.
ethz.pages.start
44
en_US
ethz.size
11 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02350 - Dep. Umweltsystemwissenschaften / Dep. of Environmental Systems Science::02720 - Institut für Integrative Biologie / Institute of Integrative Biology::03584 - Bonhoeffer, Sebastian / Bonhoeffer, Sebastian
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02350 - Dep. Umweltsystemwissenschaften / Dep. of Environmental Systems Science::02720 - Institut für Integrative Biologie / Institute of Integrative Biology::03584 - Bonhoeffer, Sebastian / Bonhoeffer, Sebastian
ethz.date.deposited
2017-06-10T19:38:25Z
ethz.source
ECIT
ethz.identifier.importid
imp593650d64842834879
ethz.ecitpid
pub:110807
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-13T08:28:52Z
ethz.rosetta.lastUpdated
2024-02-02T08:02:16Z
ethz.rosetta.versionExported
true
ethz.COinS
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