Etravirina: barrera genética y desarrollo de resistencias
Etravirine: genetic barrier and resistance development
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Llibre, José Ramón Santos, Bonaventura Clotet" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Josep M." "apellidos" => "Llibre" "email" => array:1 [ 0 => "jmllibre@flsida.org" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor1" ] ] ] 1 => array:3 [ "nombre" => "José Ramón" "apellidos" => "Santos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] ] ] 2 => array:3 [ "nombre" => "Bonaventura" "apellidos" => "Clotet" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Fundació Lluita contra la Sida, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, España" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Fundació IrsiCaixa, Badalona, Barcelona, España" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "⁎" "correspondencia" => "Autor para correspondencia." ] ] ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Etravirine: genetic barrier and resistance development" ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec137946" "palabras" => array:5 [ 0 => "Etravirina" 1 => "TMC125" 2 => "Genotipo" 3 => "Fenotipo" 4 => "Resistencia a antivirales" ] ] ] "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec137945" "palabras" => array:5 [ 0 => "Etravirine" 1 => "TMC125" 2 => "Genotype" 3 => "Phenotype" 4 => "Antiviral resistance" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<p class="elsevierStyleSimplePara elsevierViewall">A diferencia de los inhibidores de la transcriptasa inversa no análogos de nucleósidos (ITINAN) de primera generación, para desarrollar resistencia completa a etravirina (ETR) se requiere el acúmulo de varias mutaciones. Muestra una barrera intermedia frente a la aparición de resistencia parcial, y alta para el de resistencia completa. Algunas mutaciones seleccionadas por nevirapina o efavirenz impactan la actividad de ETR, siendo las más frecuentes <span class="elsevierStyleItalic">Y181C,</span><span class="elsevierStyleItalic">G190A/S,</span><span class="elsevierStyleItalic">K101E,</span><span class="elsevierStyleItalic">L100I,</span><span class="elsevierStyleItalic">Y188L</span> y <span class="elsevierStyleItalic">V90I.</span> El grado de resistencia conferida por cada una es distinto. En la actualidad se dispone de al menos 3 listados de mutaciones que otorgan la puntuación exacta a cada mutación. Estos listados se han validado con el grado de resistencia observado en fenotipos pareados, y con respuesta clínica en los estudios DUET. Los 3 <span class="elsevierStyleItalic">scores</span> muestran un elevado grado de concordancia entre ellos. ETR es, en la actualidad, uno de los antirretrovirales en los que se puede calcular de modo sencillo y con mayor precisión su actividad basándose en datos genotípicos. Las mutaciones seleccionadas tras fracasos a inhibidores de la transcriptasa inversa análogos de nucleósidos, especialmente análogos de la timidina, <span class="elsevierStyleItalic">T69D/N</span> y <span class="elsevierStyleItalic">M184I/V,</span> confieren hipersusceptibilidad frente a ETR (<span class="elsevierStyleItalic">fold</span><span class="elsevierStyleItalic">change</span> < 0,4) en hasta 1 de cada 3 muestras analizadas. Es crucial la retirada precoz de ITINAN de primera generación en pacientes con fracaso virológico para evitar el acúmulo de mutaciones que puedan comprometer la actividad del fármaco.</p>" ] "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p class="elsevierStyleSimplePara elsevierViewall">Unlike first-generation non-nucleoside reverse transcriptase inhibitors (NNRTI), to develop complete resistance to etravirine (ETR), various mutations must be accumulated. This drug shows an intermediate barrier against partial resistance and a high barrier to complete resistance. Some mutations selected by nevirapine or efavirenz affect the activity of ETR, the most frequent being <span class="elsevierStyleItalic">Y181C,</span><span class="elsevierStyleItalic">G190A/S,</span><span class="elsevierStyleItalic">K101E,</span><span class="elsevierStyleItalic">L100I,</span><span class="elsevierStyleItalic">Y188L</span> and <span class="elsevierStyleItalic">V90I</span>. The grade of resistance conferred by each mutation differs. Currently, there are at least three lists of mutations that confer an exact score to each mutation. These lists have been validated with the grade of resistance observed in paired phenotypes and with clinical response in the DUET studies. The three scores show a high degree of agreement. ETR is currently one of the antiretroviral drugs whose activity can be calculated simply and accurately on the basis of genotypic data. The mutations selected after failure to nucleoside reverse transcriptase inhibitors, thymidine analogue, <span class="elsevierStyleItalic">T69D/N</span> and <span class="elsevierStyleItalic">M184I/V</span>, confer hypersusceptibility to ETR (fold change < 0.4) in up to 1 out of every 3 samples analyzed. The early withdrawal of first-generation NNRTIs in patients with virological failure is essential to avoid the accumulation of mutations that could compromise the activity of this drug.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "Bibliografía" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:35 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "HIV-1 drug resistance mutations: an updated framework for the second decade of HAART" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R.W. Shafer" 1 => "J.M. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Octubre | 15 | 1 | 16 |
| 2024 Septiembre | 21 | 6 | 27 |
| 2024 Agosto | 16 | 2 | 18 |
| 2024 Julio | 14 | 7 | 21 |
| 2024 Junio | 12 | 4 | 16 |
| 2024 Mayo | 7 | 3 | 10 |
| 2024 Abril | 12 | 10 | 22 |
| 2024 Marzo | 10 | 6 | 16 |
| 2024 Febrero | 6 | 2 | 8 |
| 2024 Enero | 8 | 2 | 10 |
| 2023 Diciembre | 6 | 3 | 9 |
| 2023 Noviembre | 18 | 9 | 27 |
| 2023 Octubre | 23 | 8 | 31 |
| 2023 Septiembre | 18 | 4 | 22 |
| 2023 Agosto | 13 | 2 | 15 |
| 2023 Julio | 23 | 14 | 37 |
| 2023 Junio | 15 | 7 | 22 |
| 2023 Mayo | 2 | 3 | 5 |
| 2023 Abril | 9 | 4 | 13 |
| 2023 Marzo | 6 | 2 | 8 |
| 2023 Febrero | 5 | 2 | 7 |
| 2023 Enero | 6 | 2 | 8 |
| 2022 Diciembre | 6 | 4 | 10 |
| 2022 Noviembre | 11 | 5 | 16 |
| 2022 Octubre | 18 | 3 | 21 |
| 2022 Septiembre | 9 | 22 | 31 |
| 2022 Agosto | 9 | 13 | 22 |
| 2022 Julio | 9 | 6 | 15 |
| 2022 Junio | 10 | 5 | 15 |
| 2022 Mayo | 10 | 8 | 18 |
| 2022 Abril | 7 | 9 | 16 |
| 2022 Marzo | 8 | 7 | 15 |
| 2022 Febrero | 4 | 2 | 6 |
| 2022 Enero | 8 | 14 | 22 |
| 2021 Diciembre | 20 | 15 | 35 |
| 2021 Noviembre | 18 | 8 | 26 |
| 2021 Octubre | 15 | 16 | 31 |
| 2021 Septiembre | 22 | 14 | 36 |
| 2021 Agosto | 8 | 11 | 19 |
| 2021 Julio | 6 | 6 | 12 |
| 2021 Junio | 8 | 11 | 19 |
| 2021 Mayo | 12 | 20 | 32 |
| 2021 Abril | 22 | 31 | 53 |
| 2021 Marzo | 11 | 13 | 24 |
| 2021 Febrero | 10 | 18 | 28 |
| 2021 Enero | 8 | 27 | 35 |
| 2020 Diciembre | 10 | 13 | 23 |
| 2020 Noviembre | 21 | 30 | 51 |
| 2020 Octubre | 14 | 17 | 31 |
| 2020 Septiembre | 18 | 17 | 35 |
| 2020 Agosto | 4 | 2 | 6 |
| 2020 Julio | 7 | 5 | 12 |
| 2020 Junio | 9 | 11 | 20 |
| 2020 Mayo | 10 | 9 | 19 |
| 2020 Abril | 5 | 12 | 17 |
| 2020 Marzo | 21 | 7 | 28 |
| 2020 Febrero | 16 | 17 | 33 |
| 2020 Enero | 12 | 8 | 20 |
| 2019 Diciembre | 12 | 8 | 20 |
| 2019 Noviembre | 13 | 8 | 21 |
| 2019 Octubre | 18 | 9 | 27 |
| 2019 Septiembre | 18 | 21 | 39 |
| 2019 Agosto | 18 | 17 | 35 |
| 2019 Julio | 13 | 14 | 27 |
| 2019 Junio | 43 | 28 | 71 |
| 2019 Mayo | 96 | 93 | 189 |
| 2019 Abril | 54 | 67 | 121 |
| 2019 Marzo | 8 | 9 | 17 |
| 2019 Febrero | 21 | 21 | 42 |
| 2019 Enero | 13 | 14 | 27 |
| 2018 Diciembre | 15 | 9 | 24 |
| 2018 Noviembre | 24 | 9 | 33 |
| 2018 Octubre | 21 | 7 | 28 |
| 2018 Septiembre | 8 | 11 | 19 |
| 2018 Agosto | 2 | 27 | 29 |
| 2018 Julio | 6 | 32 | 38 |
| 2018 Junio | 5 | 15 | 20 |
| 2018 Mayo | 5 | 9 | 14 |
| 2018 Abril | 9 | 13 | 22 |
| 2018 Marzo | 10 | 12 | 22 |
| 2018 Febrero | 5 | 5 | 10 |
| 2018 Enero | 6 | 2 | 8 |
| 2017 Diciembre | 8 | 4 | 12 |
| 2017 Noviembre | 12 | 11 | 23 |
| 2017 Octubre | 15 | 16 | 31 |
| 2017 Septiembre | 10 | 5 | 15 |
| 2017 Agosto | 14 | 5 | 19 |
| 2017 Julio | 13 | 5 | 18 |
| 2017 Junio | 13 | 7 | 20 |
| 2017 Mayo | 12 | 7 | 19 |
| 2017 Abril | 14 | 13 | 27 |
| 2017 Marzo | 31 | 36 | 67 |
| 2017 Febrero | 25 | 25 | 50 |
| 2017 Enero | 18 | 10 | 28 |
| 2016 Diciembre | 22 | 9 | 31 |
| 2016 Noviembre | 36 | 11 | 47 |
| 2016 Octubre | 49 | 17 | 66 |
| 2016 Septiembre | 35 | 7 | 42 |
| 2016 Agosto | 41 | 16 | 57 |
| 2016 Julio | 22 | 4 | 26 |
| 2016 Junio | 33 | 14 | 47 |
| 2016 Mayo | 24 | 20 | 44 |
| 2016 Abril | 24 | 12 | 36 |
| 2016 Marzo | 21 | 7 | 28 |
| 2016 Febrero | 31 | 11 | 42 |
| 2016 Enero | 30 | 10 | 40 |
| 2015 Diciembre | 23 | 8 | 31 |
| 2015 Noviembre | 29 | 8 | 37 |
| 2015 Octubre | 22 | 11 | 33 |
| 2015 Septiembre | 30 | 12 | 42 |
| 2015 Agosto | 53 | 11 | 64 |
| 2015 Julio | 37 | 6 | 43 |
| 2015 Junio | 30 | 7 | 37 |
| 2015 Mayo | 40 | 13 | 53 |
| 2015 Abril | 24 | 10 | 34 |
| 2015 Marzo | 25 | 7 | 32 |
| 2015 Febrero | 16 | 5 | 21 |
| 2015 Enero | 32 | 8 | 40 |
| 2014 Diciembre | 35 | 6 | 41 |
| 2014 Noviembre | 37 | 2 | 39 |
| 2014 Octubre | 36 | 3 | 39 |
| 2014 Septiembre | 27 | 3 | 30 |
| 2014 Agosto | 18 | 2 | 20 |
| 2014 Julio | 21 | 2 | 23 |
| 2014 Junio | 25 | 5 | 30 |
| 2014 Mayo | 24 | 5 | 29 |
| 2014 Abril | 11 | 2 | 13 |
| 2014 Marzo | 14 | 2 | 16 |
| 2014 Febrero | 17 | 3 | 20 |
| 2014 Enero | 24 | 2 | 26 |
| 2013 Diciembre | 27 | 3 | 30 |
| 2013 Noviembre | 24 | 2 | 26 |
| 2013 Octubre | 33 | 10 | 43 |
| 2013 Septiembre | 29 | 7 | 36 |
| 2013 Agosto | 31 | 12 | 43 |
| 2013 Julio | 21 | 3 | 24 |
| 2009 Diciembre | 494 | 0 | 494 |
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