RT Journal Article
T1 Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration.
A1 Rhee, Soo-Yon
A1 Varghese, Vici
A1 Holmes, Susan P
A1 Van Zyl, Gert U
A1 Steegen, Kim
A1 Boyd, Mark A
A1 Cooper, David A
A1 Nsanzimana, Sabin
A1 Saravanan, Shanmugam
A1 Charpentier, Charlotte
A1 de Oliveira, Tulio
A1 Etiebet, Mary-Ann A
A1 Garcia, Federico
A1 Goedhals, Dominique
A1 Gomes, Perpetua
A1 Günthard, Huldrych F
A1 Hamers, Raph L
A1 Hoffmann, Christopher J
A1 Hunt, Gillian
A1 Jiamsakul, Awachana
A1 Kaleebu, Pontiano
A1 Kanki, Phyllis
A1 Kantor, Rami
A1 Kerschberger, Bernhard
A1 Marconi, Vincent C
A1 D'amour Ndahimana, Jean
A1 Ndembi, Nicaise
A1 Ngo-Giang-Huong, Nicole
A1 Rokx, Casper
A1 Santoro, Maria M
A1 Schapiro, Jonathan M
A1 Schmidt, Daniel
A1 Seu, Lillian
A1 Sigaloff, Kim C E
A1 Sirivichayakul, Sunee
A1 Skhosana, Lindiwe
A1 Sunpath, Henry
A1 Tang, Michele
A1 Yang, Chunfu
A1 Carmona, Sergio
A1 Gupta, Ravindra K
A1 Shafer, Robert W
K1 Antiretroviral therapy
K1 Drug resistance
K1 HIV-1
K1 Reverse transcriptase
K1 Tenofovir
K1 WHO-recommended first-line
AB 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.
YR 2017
FD 2017-03-19
LK http://hdl.handle.net/10668/11034
UL http://hdl.handle.net/10668/11034
LA en
DS RISalud
RD Apr 19, 2025