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2017-03-19Zeitschriftenartikel DOI: 10.1016/j.ebiom.2017.03.024
Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration
dc.contributor.authorRhee, Soo-Yon
dc.contributor.authorVarghese, Vici
dc.contributor.authorHolmes, Susan P.
dc.contributor.authorZyl, Gert U. Van
dc.contributor.authorSteegen, Kim
dc.contributor.authorBoyd, Mark A.
dc.contributor.authorCooper, David A.
dc.contributor.authorNsanzimana, Sabin
dc.contributor.authorSaravanan, Shanmugam
dc.contributor.authorCharpentier, Charlotte
dc.contributor.authorOliveira, Tulio de
dc.contributor.authorEtiebet, Mary-Ann A.
dc.contributor.authorGarcia, Federico
dc.contributor.authorGoedhals, Dominique
dc.contributor.authorGomes, Perpetua
dc.contributor.authorGünthard, Huldrych F.
dc.contributor.authorHamers, Raph L.
dc.contributor.authorHoffmann, Christopher J.
dc.contributor.authorHunt, Gillian
dc.contributor.authorJiamsakul, Awachana
dc.contributor.authorKaleebu, Pontiano
dc.contributor.authorKanki, Phyllis
dc.contributor.authorKantor, Rami
dc.contributor.authorKantor, Rami
dc.contributor.authorKerschberger, Bernhard
dc.contributor.authorSchmidt, Daniel
dc.date.accessioned2018-05-07T20:14:17Z
dc.date.available2018-05-07T20:14:17Z
dc.date.created2017-07-13
dc.date.issued2017-03-19none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/re0Fo8SOQefA/PDF/27WqDZtiFR6y6.pdf
dc.identifier.urihttp://edoc.rki.de/176904/2710
dc.description.abstractTenofovir disoproxil fumarate (TDF) genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF) on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT) mutations selected in individuals with VF on such a regimen is not known. To identify TDF regimen-associated mutations (TRAMs), we compared the proportion of each RT mutation in 2873 individuals with VF on a WHO-recommended first-line TDF-containing regimen to its proportion in a cohort of 50,803 antiretroviral-naïve individuals. To identify TRAMs specifically associated with TDF-selection pressure, we compared the proportion of each TRAM to its proportion in a cohort of 5805 individuals with VF on a first-line thymidine analog-containing regimen. We identified 83 TRAMs including 33 NRTI-associated, 40 NNRTI-associated, and 10 uncommon mutations of uncertain provenance. Of the 33 NRTI-associated TRAMs, 12 – A62V, K65R/N, S68G/N/D, K70E/Q/T, L74I, V75L, and Y115F – were more common among individuals receiving a first-line TDF-containing compared to a first-line thymidine analog-containing regimen. These 12 TDF-selected TRAMs will be important for monitoring TDF-associated transmitted drug-resistance and for determining the extent of reduced TDF susceptibility in individuals with VF on a TDF-containing regimen.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut, Infektionsepidemiologie
dc.subjectDrug resistanceeng
dc.subjectHIV-1eng
dc.subjectAntiretroviral therapyeng
dc.subjectReverse transcriptaseeng
dc.subjectTenofovireng
dc.subjectWHO-recommended first-lineeng
dc.subject.ddc610 Medizin
dc.titleMutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-10053435
dc.identifier.doi10.1016/j.ebiom.2017.03.024
dc.identifier.doihttp://dx.doi.org/10.25646/2635
local.edoc.container-titleEBioMedicine
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttp://www.sciencedirect.com/science/article/pii/S2352396417301202
local.edoc.container-publisher-nameElsevier
local.edoc.container-volume18
local.edoc.container-year2017

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