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Title: Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration.
Authors: Rhee, Soo-Yon
Varghese, Vici
Holmes, Susan P
Van Zyl, Gert U
Steegen, Kim
Boyd, Mark A
Cooper, David A
Nsanzimana, Sabin
Saravanan, Shanmugam
Charpentier, Charlotte
de Oliveira, Tulio
Etiebet, Mary-Ann A
Garcia, Federico
Goedhals, Dominique
Gomes, Perpetua
Günthard, Huldrych F
Hamers, Raph L
Hoffmann, Christopher J
Hunt, Gillian
Jiamsakul, Awachana
Kaleebu, Pontiano
Kanki, Phyllis
Kantor, Rami
Kerschberger, Bernhard
Marconi, Vincent C
D'amour Ndahimana, Jean
Ndembi, Nicaise
Ngo-Giang-Huong, Nicole
Rokx, Casper
Santoro, Maria M
Schapiro, Jonathan M
Schmidt, Daniel
Seu, Lillian
Sigaloff, Kim C E
Sirivichayakul, Sunee
Skhosana, Lindiwe
Sunpath, Henry
Tang, Michele
Yang, Chunfu
Carmona, Sergio
Gupta, Ravindra K
Shafer, Robert W
Keywords: Antiretroviral therapy;Drug resistance;HIV-1;Reverse transcriptase;Tenofovir;WHO-recommended first-line
metadata.dc.subject.mesh: Drug Resistance, Viral
HIV Infections
HIV Reverse Transcriptase
Reverse Transcriptase Inhibitors
Treatment Failure
Viral Load
World Health Organization
Issue Date: 19-Mar-2017
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.
metadata.dc.identifier.doi: 10.1016/j.ebiom.2017.03.024
Appears in Collections:Producción 2020

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