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dc.contributor.author
Kühnert, Denise
dc.contributor.author
Kouyos, Roger
dc.contributor.author
Shirreff, George
dc.contributor.author
Pečerska, Jūlija
dc.contributor.author
Scherrer, Alexandra U.
dc.contributor.author
Böni, Jürg
dc.contributor.author
Yerly, Sabine
dc.contributor.author
Klimkait, Thomas
dc.contributor.author
Aubert, Vincent
dc.contributor.author
Günthard, Huldrych F.
dc.contributor.author
Stadler, Tanja
dc.contributor.author
Bonhoeffer, Sebastian
dc.contributor.author
Swiss HIV Cohort Study
dc.date.accessioned
2018-11-06T09:24:53Z
dc.date.available
2018-03-15T03:57:01Z
dc.date.available
2018-04-04T10:16:06Z
dc.date.available
2018-11-06T09:24:53Z
dc.date.issued
2018-02
dc.identifier.other
10.1371/journal.ppat.1006895
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/250011
dc.identifier.doi
10.3929/ethz-b-000250011
dc.description.abstract
Drug resistant HIV is a major threat to the long-term efficacy of antiretroviral treatment. Around 10% of ART-naïve patients in Europe are infected with drug-resistant HIV type 1. Hence it is important to understand the dynamics of transmitted drug resistance evolution. Thanks to routinely performed drug resistance tests, HIV sequence data is increasingly available and can be used to reconstruct the phylogenetic relationship among viral lineages. In this study we employ a phylodynamic approach to quantify the fitness costs of major resistance mutations in the Swiss HIV cohort. The viral phylogeny reflects the transmission tree, which we model using stochastic birth–death-sampling processes with two types: hosts infected by a sensitive or resistant strain. This allows quantification of fitness cost as the ratio between transmission rates of hosts infected by drug resistant strains and transmission rates of hosts infected by drug sensitive strains. The resistance mutations 41L, 67N, 70R, 184V, 210W, 215D, 215S and 219Q (nRTI-related) and 103N, 108I, 138A, 181C, 190A (NNRTI-related) in the reverse trancriptase and the 90M mutation in the protease gene are included in this study. Among the considered resistance mutations, only the 90M mutation in the protease gene was found to have significantly higher fitness than the drug sensitive strains. The following mutations associated with resistance to reverse transcriptase inhibitors were found to be less fit than the sensitive strains: 67N, 70R, 184V, 219Q. The highest posterior density intervals of the transmission ratios for the remaining resistance mutations included in this study all included 1, suggesting that these mutations do not have a significant effect on viral transmissibility within the Swiss HIV cohort. These patterns are consistent with alternative measures of the fitness cost of resistance mutations. Overall, we have developed and validated a novel phylodynamic approach to estimate the transmission fitness cost of drug resistance mutations.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Public Library of Science (PLoS)
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Quantifying the fitness cost of HIV-1 drug resistance mutations through phylodynamics
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2018-02-20
ethz.journal.title
PLoS pathogens
ethz.journal.volume
14
en_US
ethz.journal.issue
2
en_US
ethz.pages.start
e1006895
en_US
ethz.size
16 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Lawrence, KS
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::09490 - Stadler, Tanja / Stadler, Tanja
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
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::09490 - Stadler, Tanja / Stadler, Tanja
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
2018-03-15T03:57:02Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2018-04-04T10:16:15Z
ethz.rosetta.lastUpdated
2019-01-03T09:16:45Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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