1. Mutational correlates of virological failure in individuals receiving a WHO-recommended tenofovir-containing first-line regimen: An international collaboration
- Author
-
Rhee, S.Y. (Soo Yoon), Varghese, V. (Vici), Holmes, S.P. (Susan P.), Van Zyl, G.U. (Gert U.), Steegen, K. (Kim), Boyd, M.A. (Mark A.), Cooper, D.A. (David), Nsanzimana, S. (Sabin), Saravanan, S. (Shanmugam), Charpentier, C. (Charlotte), Oliveira, T. (Tulio) de, Etiebet, M.A.A. (Mary-Ann A.), Garcia, F., Goedhals, D., Gomes, P. (Perpetua), Günthard, H.F., Hamers, R.L. (Raph), Hoffmann, C.J. (Christopher J), Hunt, G.M. (Gillian M.), Jiamsakul, A. (Awachana), Kaleebu, P. (Pontiano), Kanki, P.J., Kantor, R. (Rami), Kerschberger, B., Marconi, V.C., D'amour Ndahimana, J. (Jean), Ndembi, N. (Nicaise), Ngo-Giang-Huong, N. (Nicole), Rokx, C. (Casper), Santoro, M.M. (Maria), Schapiro, J.M. (Jonathan), Schmidt, D., Seu, L. (Lillian), Sigaloff, K.C. (Kim), Sirivichayakul, S. (Sunee), Skhosana, L. (Lindiwe), Sunpath, H., Tang, M., Yang, C. (Chunfu), Carmona, S. (Sergio), Gupta, R.K. (Ravindra K.), Shafer, R.W. (Robert), Rhee, S.Y. (Soo Yoon), Varghese, V. (Vici), Holmes, S.P. (Susan P.), Van Zyl, G.U. (Gert U.), Steegen, K. (Kim), Boyd, M.A. (Mark A.), Cooper, D.A. (David), Nsanzimana, S. (Sabin), Saravanan, S. (Shanmugam), Charpentier, C. (Charlotte), Oliveira, T. (Tulio) de, Etiebet, M.A.A. (Mary-Ann A.), Garcia, F., Goedhals, D., Gomes, P. (Perpetua), Günthard, H.F., Hamers, R.L. (Raph), Hoffmann, C.J. (Christopher J), Hunt, G.M. (Gillian M.), Jiamsakul, A. (Awachana), Kaleebu, P. (Pontiano), Kanki, P.J., Kantor, R. (Rami), Kerschberger, B., Marconi, V.C., D'amour Ndahimana, J. (Jean), Ndembi, N. (Nicaise), Ngo-Giang-Huong, N. (Nicole), Rokx, C. (Casper), Santoro, M.M. (Maria), Schapiro, J.M. (Jonathan), Schmidt, D., Seu, L. (Lillian), Sigaloff, K.C. (Kim), Sirivichayakul, S. (Sunee), Skhosana, L. (Lindiwe), Sunpath, H., Tang, M., Yang, C. (Chunfu), Carmona, S. (Sergio), Gupta, R.K. (Ravindra K.), and Shafer, R.W. (Robert)
- 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 a
- Published
- 2017
- Full Text
- View/download PDF