Mutational correlates of virological failure in individuals receiving a WHO-recommended tenofovir-containing first-line regimen : an international collaboration

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dc.contributor.authorRhee, Soo-Yonen_ZA
dc.contributor.authorVarghese, Vicien_ZA
dc.contributor.authorHolmes, Susan P.en_ZA
dc.contributor.authorVan Zyl, Gert U.en_ZA
dc.contributor.authorSteegen, Kimen_ZA
dc.contributor.authorBoyd, Mark A.en_ZA
dc.contributor.authorCooper, David A.en_ZA
dc.contributor.authorNsanzimana, Sabinen_ZA
dc.contributor.authorSaravanan, Shanmugamen_ZA
dc.contributor.authorCharpentier, Charlotteen_ZA
dc.contributor.authorDe Oliveira, Tulioen_ZA
dc.contributor.authorEtiebet, Mary-Ann A.en_ZA
dc.contributor.authorGarcia, Federicoen_ZA
dc.contributor.authorGoedhals, Dominiqueen_ZA
dc.contributor.authorGomes, Perpetuaen_ZA
dc.contributor.authorGunthard, Huldrych F.en_ZA
dc.contributor.authorHamers, Raph L.en_ZA
dc.contributor.authorHoffmann, Christopher J.en_ZA
dc.contributor.authorHunt, Gillianen_ZA
dc.contributor.authorJiamsakul, Awachanaen_ZA
dc.contributor.authorKaleebu, Pontianoen_ZA
dc.contributor.authorKanki, Phyllisen_ZA
dc.contributor.authorKantor, Ramien_ZA
dc.contributor.authorKerschberger, Bernharden_ZA
dc.contributor.authorMarconi, Vincent C.en_ZA
dc.contributor.authorNdahimana, Jean D'amouren_ZA
dc.contributor.authorNdembi, Nicaiseen_ZA
dc.contributor.authorNgo-Giang-Huong, Nicoleen_ZA
dc.contributor.authorRokx, Casperen_ZA
dc.contributor.authorSantoro, Maria M.en_ZA
dc.contributor.authorSchapiro, Jonathan M.en_ZA
dc.contributor.authorSchmidt, Danielen_ZA
dc.contributor.authorSeu, Lillianen_ZA
dc.contributor.authorSigaloff, Kim C. E.en_ZA
dc.contributor.authorSirivichayakul, Suneeen_ZA
dc.contributor.authorSkhosana, Lindiween_ZA
dc.contributor.authorSunpath, Henryen_ZA
dc.contributor.authorTang, Micheleen_ZA
dc.contributor.authorYang, Chunfuen_ZA
dc.contributor.authorCarmona, Sergioen_ZA
dc.contributor.authorGupta, Ravindra K.en_ZA
dc.contributor.authorShafer, Robert W.en_ZA
dc.date.accessioned2018-08-17T08:47:18Z
dc.date.available2018-08-17T08:47:18Z
dc.date.issued2017
dc.descriptionCITATION: Rhee, S. Y., et al. 2017. Mutational correlates of virological failure in individuals receiving a WHO-recommended tenofovir-containing first-line regimen : an international collaboration. EBioMedicine, 18: 225-235, doi:10.1016/j.ebiom.2017.03.024.
dc.descriptionThe original publication is available at https://www.sciencedirect.com
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.en_ZA
dc.description.urihttps://www.sciencedirect.com/science/article/pii/S2352396417301202?via%3Dihub
dc.description.versionPublisher's version
dc.format.extent11 pages
dc.identifier.citationRhee, S. Y., et al. 2017. Mutational correlates of virological failure in individuals receiving a WHO-recommended tenofovir-containing first-line regimen : an international collaboration. EBioMedicine, 18: 225-235, doi:10.1016/j.ebiom.2017.03.024
dc.identifier.issn2352-3964 (online)
dc.identifier.otherdoi:10.1016/j.ebiom.2017.03.024
dc.identifier.otherdoi:10.1016/j.ebiom.2017.03.024
dc.identifier.urihttp://hdl.handle.net/10019.1/104277
dc.language.isoen_ZAen_ZA
dc.publisherElsevier
dc.rights.holderAuthors retain copyright
dc.subjectHighly active antiretroviral therapyen_ZA
dc.subjectReverse transcriptaseen_ZA
dc.titleMutational correlates of virological failure in individuals receiving a WHO-recommended tenofovir-containing first-line regimen : an international collaborationen_ZA
dc.typeArticleen_ZA
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