BACKGROUND: The human immunodeficiency virus type 1 reverse-transcriptase mutation K65R is a single-point mutation that has become more frequent after increased use of tenofovir disoproxil fumarate (TDF). We aimed to identify predictors for the emergence of K65R, using clinical data and genotypic resistance tests from the Swiss HIV Cohort Study. METHODS: A total of 222 patients with genotypic resistance tests performed while receiving treatment with TDF-containing regimens were stratified by detectability of K65R (K65R group, 42 patients; undetected K65R group, 180 patients). Patient characteristics at start of that treatment were analyzed. RESULTS: In an adjusted logistic regression, TDF treatment with nonnucleoside reverse-transcriptase inhibitors and/or didanosine was associated with the emergence of K65R, whereas the presence of any of the thymidine analogue mutations D67N, K70R, T215F, or K219E/Q was protective. The previously undescribed mutational pattern K65R/G190S/Y181C was observed in 6 of 21 patients treated with efavirenz and TDF. Salvage therapy after TDF treatment was started for 36 patients with K65R and for 118 patients from the wild-type group. Proportions of patients attaining human immunodeficiency virus type 1 loads <50 copies/mL after 24 weeks of continuous treatment were similar for the K65R group (44.1%; 95% confidence interval, 27.2%-62.1%) and the wild-type group (51.9%; 95% confidence interval, 42.0%-61.6%). CONCLUSIONS: In settings where thymidine analogue mutations are less likely to be present, such as at start of first-line therapy or after extended treatment interruptions, combinations of TDF with other K65R-inducing components or with efavirenz or nevirapine may carry an enhanced risk of the emergence of K65R. The finding of a distinct mutational pattern selected by treatment with TDF and efavirenz suggests a potential fitness interaction between K65R and nonnucleoside reverse-transcriptase inhibitor-induced mutations.
BACKGROUND: The human immunodeficiency virus type 1 reverse-transcriptase mutation K65R is a single-point mutation that has become more frequent after increased use of tenofovir disoproxil fumarate (TDF). We aimed to identify predictors for the emergence of K65R, using clinical data and genotypic resistance tests from the Swiss HIV Cohort Study. METHODS: A total of 222 patients with genotypic resistance tests performed while receiving treatment with TDF-containing regimens were stratified by detectability of K65R (K65R group, 42 patients; undetected K65R group, 180 patients). Patient characteristics at start of that treatment were analyzed. RESULTS: In an adjusted logistic regression, TDF treatment with nonnucleoside reverse-transcriptase inhibitors and/or didanosine was associated with the emergence of K65R, whereas the presence of any of the thymidine analogue mutations D67N, K70R, T215F, or K219E/Q was protective. The previously undescribed mutational pattern K65R/G190S/Y181C was observed in 6 of 21 patients treated with efavirenz and TDF. Salvage therapy after TDF treatment was started for 36 patients with K65R and for 118 patients from the wild-type group. Proportions of patients attaining human immunodeficiency virus type 1 loads <50 copies/mL after 24 weeks of continuous treatment were similar for the K65R group (44.1%; 95% confidence interval, 27.2%-62.1%) and the wild-type group (51.9%; 95% confidence interval, 42.0%-61.6%). CONCLUSIONS: In settings where thymidine analogue mutations are less likely to be present, such as at start of first-line therapy or after extended treatment interruptions, combinations of TDF with other K65R-inducing components or with efavirenz or nevirapine may carry an enhanced risk of the emergence of K65R. The finding of a distinct mutational pattern selected by treatment with TDF and efavirenz suggests a potential fitness interaction between K65R and nonnucleoside reverse-transcriptase inhibitor-induced mutations.
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Authors: Victoria A Johnson; Vincent Calvez; Huldrych F Günthard; Roger Paredes; Deenan Pillay; Robert Shafer; Annemarie M Wensing; Douglas D Richman Journal: Top Antivir Med Date: 2011-11
Authors: K Theys; J Vercauteren; J Snoeck; M Zazzi; R J Camacho; C Torti; E Schülter; B Clotet; A Sönnerborg; A De Luca; Z Grossman; D Struck; A-M Vandamme; A B Abecasis Journal: Antimicrob Agents Chemother Date: 2012-11-26 Impact factor: 5.191
Authors: Christa R Nevin; Jiatao Ye; Inmaculada Aban; Michael J Mugavero; David Jackson; Hui-Yi Lin; Jeroan Allison; James L Raper; Michael S Saag; James H Willig Journal: AIDS Res Hum Retroviruses Date: 2011-03-21 Impact factor: 2.205
Authors: Annemarie M Wensing; Vincent Calvez; Francesca Ceccherini-Silberstein; Charlotte Charpentier; Huldrych F Günthard; Roger Paredes; Robert W Shafer; Douglas D Richman Journal: Top Antivir Med Date: 2019-09
Authors: Gilberto Betancor; César Garriga; Maria C Puertas; María Nevot; Lourdes Anta; José L Blanco; M Jesús Pérez-Elías; Carmen de Mendoza; Miguel A Martínez; Javier Martinez-Picado; Luis Menéndez-Arias; José Antonio Iribarren; Estrella Caballero; Esteban Ribera; Josep Maria Llibre; Bonaventura Clotet; Angels Jaén; David Dalmau; José María Gatel; Joaquín Peraire; Francesc Vidal; Carmen Vidal; Melchor Riera; Juan Córdoba; José López Aldeguer; María José Galindo; Félix Gutiérrez; Marta Álvarez; Federico García; Pilar Pérez-Romero; Pompeyo Viciana; Manuel Leal; José Carlos Palomares; Juan Antonio Pineda; Isabel Viciana; Jesús Santos; Patricia Rodríguez; Juan Luis Gómez Sirvent; Carolina Gutiérrez; Santiago Moreno; Mayte Pérez-Olmeda; José Alcamí; Carmen Rodríguez; Jorge del Romero; Angelina Cañizares; José Pedreira; Celia Miralles; Antonio Ocampo; Luis Morano; Antonio Aguilera; Carolina Garrido; Gustavo Manuzza; Eva Poveda; Vicente Soriano Journal: Retrovirology Date: 2012-08-13 Impact factor: 4.602