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dc.contributor.authorRhee, SY
dc.contributor.authorVarghese, V
dc.contributor.authorHolmes, SP
dc.contributor.authorVan Zyl, GU
dc.contributor.authorSteegen, K
dc.contributor.authorBoyd, MA
dc.contributor.authorCooper, DA
dc.contributor.authorNsanzimana, S
dc.contributor.authorSaravanan, S
dc.contributor.authorCharpentier, C
dc.contributor.authorde Oliveira, T
dc.contributor.authorEtiebet, MA
dc.contributor.authorGarcia, F
dc.contributor.authorGoedhals, D
dc.contributor.authorGomes, P
dc.contributor.authorGünthard, HF
dc.contributor.authorHamers, RL
dc.contributor.authorHoffmann, CJ
dc.contributor.authorHunt, G
dc.contributor.authorJiamsakul, A
dc.contributor.authorKaleebu, P
dc.contributor.authorKanki, P
dc.contributor.authorKantor, R
dc.contributor.authorKerschberger, B
dc.contributor.authorMarconi, VC
dc.contributor.authorD'amour Ndahimana, J
dc.contributor.authorNdembi, N
dc.contributor.authorNgo-Giang-Huong, N
dc.contributor.authorRokx, C
dc.contributor.authorSantoro, MM
dc.contributor.authorSchapiro, JM
dc.contributor.authorSchmidt, D
dc.contributor.authorSeu, L
dc.contributor.authorSigaloff, KCE
dc.contributor.authorSirivichayakul, S
dc.contributor.authorSkhosana, L
dc.contributor.authorSunpath, H
dc.contributor.authorTang, M
dc.contributor.authorYang, C
dc.contributor.authorCarmona, S
dc.contributor.authorGupta, RK
dc.contributor.authorShafer, RW
dc.date.accessioned2017-04-19T16:32:22Z
dc.date.available2017-04-19T16:32:22Z
dc.date.issued2017-03-19
dc.date.submitted2017-04-12
dc.identifier.citationMutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration 2017 EBioMedicineen
dc.identifier.issn2352-3964
dc.identifier.pmid28365230
dc.identifier.doi10.1016/j.ebiom.2017.03.024
dc.identifier.urihttp://hdl.handle.net/10144/618895
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.
dc.language.isoenen
dc.publisherElsevieren
dc.rightsArchived with thanks to EBioMedicineen
dc.titleMutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaborationen
dc.identifier.journalEBioMedicineen
refterms.dateFOA2019-03-04T13:20:44Z
html.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.


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