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; +32 more... 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 CE; Sirivichayakul, Sunee; Skhosana, Lindiwe; Sunpath, Henry; Tang, Michele; Yang, Chunfu; Carmona, Sergio; Gupta, Ravindra K; Shafer, Robert W; (2017) Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration. EBioMedicine, 18. pp. 225-235. ISSN 2352-3964 DOI: https://doi.org/10.1016/j.ebiom.2017.03.024
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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.
Item Type | Article |
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Faculty and Department | MRC Uganda > UG-HIV Care |
PubMed ID | 28365230 |
ISI | 402105100033 |
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