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

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.

journal_name

EBioMedicine

journal_title

EBioMedicine

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,

doi

10.1016/j.ebiom.2017.03.024

subject

Has Abstract

pub_date

2017-04-01 00:00:00

pages

225-235

issn

2352-3964

pii

S2352-3964(17)30120-2

journal_volume

18

pub_type

杂志文章

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