Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration

Hdl Handle:
http://hdl.handle.net/10144/618895
Title:
Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration
Authors:
Rhee, SY; Varghese, V; Holmes, SP; Van Zyl, GU; Steegen, K; Boyd, MA; Cooper, DA; Nsanzimana, S; Saravanan, S; Charpentier, C; de Oliveira, T; Etiebet, MA; Garcia, F; Goedhals, D; Gomes, P; Günthard, HF; Hamers, RL; Hoffmann, CJ; Hunt, G; Jiamsakul, A; Kaleebu, P; Kanki, P; Kantor, R; Kerschberger, B; Marconi, VC; D'amour Ndahimana, J; Ndembi, N; Ngo-Giang-Huong, N; Rokx, C; Santoro, MM; Schapiro, JM; Schmidt, D; Seu, L; Sigaloff, KCE; Sirivichayakul, S; Skhosana, L; Sunpath, H; Tang, M; Yang, C; Carmona, S; Gupta, RK; Shafer, RW
Journal:
EBioMedicine
Abstract:
Tenofovir 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.
Publisher:
Elsevier
Issue Date:
19-Mar-2017
URI:
http://hdl.handle.net/10144/618895
DOI:
10.1016/j.ebiom.2017.03.024
PubMed ID:
28365230
Submitted date:
2017-04-12
Language:
en
ISSN:
2352-3964
Appears in Collections:
HIV/AIDS

Full metadata record

DC FieldValue Language
dc.contributor.authorRhee, SYen
dc.contributor.authorVarghese, Ven
dc.contributor.authorHolmes, SPen
dc.contributor.authorVan Zyl, GUen
dc.contributor.authorSteegen, Ken
dc.contributor.authorBoyd, MAen
dc.contributor.authorCooper, DAen
dc.contributor.authorNsanzimana, Sen
dc.contributor.authorSaravanan, Sen
dc.contributor.authorCharpentier, Cen
dc.contributor.authorde Oliveira, Ten
dc.contributor.authorEtiebet, MAen
dc.contributor.authorGarcia, Fen
dc.contributor.authorGoedhals, Den
dc.contributor.authorGomes, Pen
dc.contributor.authorGünthard, HFen
dc.contributor.authorHamers, RLen
dc.contributor.authorHoffmann, CJen
dc.contributor.authorHunt, Gen
dc.contributor.authorJiamsakul, Aen
dc.contributor.authorKaleebu, Pen
dc.contributor.authorKanki, Pen
dc.contributor.authorKantor, Ren
dc.contributor.authorKerschberger, Ben
dc.contributor.authorMarconi, VCen
dc.contributor.authorD'amour Ndahimana, Jen
dc.contributor.authorNdembi, Nen
dc.contributor.authorNgo-Giang-Huong, Nen
dc.contributor.authorRokx, Cen
dc.contributor.authorSantoro, MMen
dc.contributor.authorSchapiro, JMen
dc.contributor.authorSchmidt, Den
dc.contributor.authorSeu, Len
dc.contributor.authorSigaloff, KCEen
dc.contributor.authorSirivichayakul, Sen
dc.contributor.authorSkhosana, Len
dc.contributor.authorSunpath, Hen
dc.contributor.authorTang, Men
dc.contributor.authorYang, Cen
dc.contributor.authorCarmona, Sen
dc.contributor.authorGupta, RKen
dc.contributor.authorShafer, RWen
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.en
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

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