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array:23 [ "pii" => "S0025775309005569" "issn" => "00257753" "doi" => "10.1016/j.medcli.2009.02.020" "estado" => "S300" "fechaPublicacion" => "2010-04-03" "aid" => "345" "copyright" => "Elsevier España, S.L.. Todos los derechos reservados" "copyrightAnyo" => "2008" "documento" => "article" "crossmark" => 0 "subdocumento" => "sco" "cita" => "Med Clin. 2010;134:399-401" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1546 "formatos" => array:3 [ "EPUB" => 7 "HTML" => 1269 "PDF" => 270 ] ] "itemSiguiente" => array:18 [ "pii" => "S0025775309016443" "issn" => "00257753" "doi" => "10.1016/j.medcli.2009.07.053" "estado" => "S300" "fechaPublicacion" => "2010-04-03" "aid" => "810" "copyright" => "Elsevier España, S.L." "documento" => "article" "crossmark" => 0 "subdocumento" => "sco" "cita" => "Med Clin. 2010;134:402-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2300 "formatos" => array:3 [ "EPUB" => 7 "HTML" => 1987 "PDF" => 306 ] ] "es" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Nota clínica</span>" "titulo" => "Utilidad del tratamiento de sustitución enzimática en la enfermedad de Fabry" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "402" "paginaFinal" => "405" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Utility of enzyme replacement therapy in Fabry disease" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Juan Manuel Politei, Alberto Dubrovsky" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Juan Manuel" "apellidos" => "Politei" ] 1 => array:2 [ "nombre" => "Alberto" "apellidos" => "Dubrovsky" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775309016443?idApp=UINPBA00004N" "url" => "/00257753/0000013400000009/v1_201304301843/S0025775309016443/v1_201304301843/es/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S0025775310000199" "issn" => "00257753" "doi" => "10.1016/j.medcli.2010.01.001" "estado" => "S300" "fechaPublicacion" => "2010-04-03" "aid" => "814" "copyright" => "Elsevier España, S.L." "documento" => "article" "crossmark" => 0 "subdocumento" => "sco" "cita" => "Med Clin. 2010;134:396-8" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2527 "formatos" => array:3 [ "EPUB" => 7 "HTML" => 2174 "PDF" => 346 ] ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "¿Qué medida antropométrica de exceso de peso discrimina mejor el riesgo cardiovascular?" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "396" "paginaFinal" => "398" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Which of the anthropometric measures to define excess weight is the best discriminator of cardiovascular risk?" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "María Natividad Moreira Andrés" "autores" => array:1 [ 0 => array:3 [ "Iniciales" => "M.N." "nombre" => "María Natividad" "apellidos" => "Moreira Andrés" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775310000199?idApp=UINPBA00004N" "url" => "/00257753/0000013400000009/v1_201304301843/S0025775310000199/v1_201304301843/es/main.assets" ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Infección por el virus de la inmunodeficiencia humana tipo 1: errores irreversibles que no deberíamos volver a cometer" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "399" "paginaFinal" => "401" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "José M. Gatell Artigas" "autores" => array:1 [ 0 => array:4 [ "Iniciales" => "J.M." "nombre" => "José M." "apellidos" => "Gatell Artigas" "email" => array:1 [ 0 => "gatell0@attglobal.net" ] ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Servicio de Infecciones, Hospital Clínic-IDIBAPS, Universidad de Barcelona, Barcelona, España" ] ] ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "HIV infection. Irreversible mistakes not to be repeated" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p class="elsevierStylePara elsevierViewall">Durante los aproximadamente 25 años de historia de la infección por el virus de la inmunodeficiencia humana (VIH) tipo <span class="elsevierStyleSmallCaps">i</span> (VIH-1) y del síndrome de inmunodeficiencia adquirida<a class="elsevierStyleCrossRef" href="#bib1"><span class="elsevierStyleSup">1</span></a> hemos cometido muchos errores. Algunos han sido irreversibles y no deberían repetirse. No deberíamos mimetizar otros en la actitud diagnosticoterapéutica y en el tratamiento de otras infecciones como las producidas por los virus de la hepatitis B y de la hepatitis C<a class="elsevierStyleCrossRefs" href="#bib2"><span class="elsevierStyleSup">2–4</span></a>. Finalmente, deberíamos evitarlos en los países en vías de desarrollo, en los que más del 90% de los pacientes están infectados por VIH-1, sobre todo ahora que la posibilidad de que puedan acceder al tratamiento va dejando de ser una quimera. A mediados de la década de 1980 tuvimos una tendencia a minimizar la epidemia («… otras enfermedades matan más…»), contra toda prueba aceptamos que la transmisión se restringía a las llamadas 4 haches (Haití, heroína, hemofilia y homosexualidad masculina), se retrasó el cribado en los bancos de sangre y cuando a finales de la década de 1980 aparecieron los primeros antirretrovíricos<a class="elsevierStyleCrossRefs" href="#bib5"><span class="elsevierStyleSup">5,6</span></a> no aplicamos los principios del tratamiento de enfermedades como la tuberculosis<a class="elsevierStyleCrossRefs" href="#bib7"><span class="elsevierStyleSup">7–10</span></a> y utilizamos de forma secuencial tratamientos de barrera genética baja.</p><p class="elsevierStylePara elsevierViewall">Infectarse por VIH-1, incluso en el año 2008, sigue siendo un error grave e irreversible<a class="elsevierStyleCrossRefs" href="#bib11"><span class="elsevierStyleSup">11,12</span></a>. La esperanza de vida de los pacientes infectados, a pesar de lo mucho que ha mejorado, todavía dista bastante de la estimada para la población general de la misma edad y sexo<a class="elsevierStyleCrossRef" href="#bib13"><span class="elsevierStyleSup">13</span></a>. Cuando una persona se ha infectado e inicia el tratamiento en una fase avanzada de la enfermedad, en muchos casos puede también ser una situación irreversible<a class="elsevierStyleCrossRefs" href="#bib12"><span class="elsevierStyleSup">12,14</span></a>. A pesar de esto, más del 40% de los pacientes tiene una cifra plasmática de linfocitos CD4+ inferior a 200×10<span class="elsevierStyleSup">6</span>/l la primera vez que contacta con el sistema sanitario<a class="elsevierStyleCrossRef" href="#bib12"><span class="elsevierStyleSup">12</span></a>. Algunos nunca recuperarán de forma «completa» esta cifra y otros desarrollarán complicaciones mientras no la hayan superado<a class="elsevierStyleCrossRef" href="#bib15"><span class="elsevierStyleSup">15</span></a>.</p><p class="elsevierStylePara elsevierViewall">Disponemos de más de 20 fármacos comercializados y de múltiples combinaciones posibles. Iniciar el tratamiento con fármacos asociados a complicaciones graves o letales, aunque la incidencia sea muy baja, puede también ser un error irreversible. Lo mismo es cierto para aquellos fármacos o combinaciones con un mayor potencial para asociarse al desarrollo de una lipoatrofia<a class="elsevierStyleCrossRefs" href="#bib16"><span class="elsevierStyleSup">16–19</span></a>. La reversión de la lipoatrofia es muy lenta, si es que la hay, y puede ser imposible si se ha sobrepasado un determinado umbral de pérdida de grasa<a class="elsevierStyleCrossRefs" href="#bib19"><span class="elsevierStyleSup">19,20</span></a>. La replicación vírica activa es perjudicial para el huésped no sólo por su capacidad, directa o indirecta, de lisar linfocitos CD4+, sino también por sus efectos inflamatorios y por mantenerse una hiperactivación sostenida del sistema inmunitario<a class="elsevierStyleCrossRef" href="#bib21"><span class="elsevierStyleSup">21</span></a>. Por tanto, los tratamientos deben empezarse de forma precoz (quizás a partir del mismo momento del diagnóstico de la infección por VIH) y no deben interrumpirse salvo que haya un motivo muy justificado<a class="elsevierStyleCrossRefs" href="#bib21"><span class="elsevierStyleSup">21–24</span></a>.</p><p class="elsevierStylePara elsevierViewall">En el año 2008 sólo son aceptables las pautas del tratamiento inicial que potencialmente tengan una tasa de respuesta superior al 90% al año<a class="elsevierStyleCrossRef" href="#bib25"><span class="elsevierStyleSup">25</span></a>. En las dos terceras partes de los pocos pacientes en los que se produce un fallo virológico se seleccionará una o varias mutaciones de resistencia<a class="elsevierStyleCrossRefs" href="#bib26"><span class="elsevierStyleSup">26–29</span></a>. Estas mutaciones o combinaciones de mutaciones quedan «archivadas» en el genoma del virus y pueden reaparecer rápidamente si se reintroduce la presión farmacológica que las seleccionó<a class="elsevierStyleCrossRef" href="#bib30"><span class="elsevierStyleSup">30</span></a>. Continuar con la misma presión farmacológica (no cambiar el tratamiento) conducirá a la acumulación más o menos rápida de mutaciones de resistencia con patrones cada vez más complejos<a class="elsevierStyleCrossRefs" href="#bib31"><span class="elsevierStyleSup">31,32</span></a>. Las resistencias suelen (o al menos pueden) ser cruzadas con todos los fármacos de la misma familia, incluso con aquellos que todavía no se han descubierto<a class="elsevierStyleCrossRef" href="#bib29"><span class="elsevierStyleSup">29</span></a>. Los tratamientos de rescate han de consistir en un mínimo de 3 fármacos activos y su objetivo irrenunciable ha de ser alcanzar una carga vírica indetectable<a class="elsevierStyleCrossRef" href="#bib24"><span class="elsevierStyleSup">24</span></a>. La recuperación de linfocitos CD4+ como respuesta al tratamiento no siempre es una imagen «en espejo» de la reducción de la carga vírica, aunque hasta ahora las diferencias asociadas a distintos regímenes terapéuticos han sido escasas, posiblemente multifactoriales y desconocemos su significado clínico, si es que tiene alguno<a class="elsevierStyleCrossRef" href="#bib33"><span class="elsevierStyleSup">33</span></a>. Finalmente, ninguna mujer en edad fértil e infectada por VIH debería tomar fármacos potencialmente teratogénicos si no toma precauciones para evitar el embarazo. Si éste se produce, la tasa de transmisión maternofetal debería ser prácticamente nula<a class="elsevierStyleCrossRefs" href="#bib34"><span class="elsevierStyleSup">34–36</span></a>.</p><p class="elsevierStylePara elsevierViewall">En el campo del tratamiento del VIH-1 se han producido avances considerables desde 1997, avances que se han consolidado en los últimos 2 a 3 años. Esto ha sido así gracias, al menos en parte, a que las decisiones se han basado en datos científicos sólidos, la mayoría obtenidos en estudios prospectivos y aleatorizados<a class="elsevierStyleCrossRefs" href="#bib37"><span class="elsevierStyleSup">37–39</span></a>. Los datos obtenidos a partir de análisis de cohortes son muy valiosos para definir la historia natural de la enfermedad, pero pueden inducir a errores irreversibles si con ellos se pretende tomar decisiones terapéuticas. Finalmente, las percepciones, por muy extendidas que estén, no pueden sustituir a los hechos probados o admitirse como hechos probados. Durante muchos años hemos sostenido que la actitud diagnosticoterapéutica del paciente infectado por VIH y el tratamiento antirretrovírico requieren un grado importante de especialización. Este es un hecho demostrado, pero a medida que nuestros pacientes sobrevivan a largo plazo y, por tanto, envejezcan (en el Hospital Clínic de Barcelona más del 50% de los cerca de 4.000 pacientes que controlamos tiene más de 50 años) cada vez serán más necesarios el médico de familia y el internista general<a class="elsevierStyleCrossRef" href="#bib40"><span class="elsevierStyleSup">40</span></a>.</p><p class="elsevierStylePara elsevierViewall">Por último, en los países en vías de desarrollo se ha conseguido que cerca del 30% de los pacientes que necesita tratamiento antirretrovírico ya lo esté recibiendo. Pero esta cifra relativamente optimista esconde potenciales errores irreversibles. Están utilizando aquellas combinaciones de medicamentos que en el mundo desarrollado hemos desechado por su potencial de producir lipodistrofia<a class="elsevierStyleCrossRef" href="#bib41"><span class="elsevierStyleSup">41</span></a>. Monitorizan la respuesta al tratamiento utilizando exclusivamente datos clínicos, lo que conduce a cambios innecesarios o a continuar con la misma presión farmacológica en presencia de un fallo virológico<a class="elsevierStyleCrossRef" href="#bib42"><span class="elsevierStyleSup">42</span></a>. Y, a menudo, no se cambia el tratamiento antirretrovírico (por falta de medicamentos alternativos de segunda línea) en presencia de fallos virológicos, lo que conduce a la acumulación y a la diseminación de mutaciones de resistencia<a class="elsevierStyleCrossRefs" href="#bib43"><span class="elsevierStyleSup">43,44</span></a>. Finalmente, se siguen tolerando tasas de transmisión maternofetal inaceptablemente altas por no usar las pautas adecuadas durante el período de tiempo necesario en las mujeres embarazadas y mientras dura la lactancia materna<a class="elsevierStyleCrossRefs" href="#bib34"><span class="elsevierStyleSup">34,35,45–48</span></a>.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "Bibliografía" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:48 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Opportunistic infection in previously healthy women. Initial manifestations of a community-acquired cellular immunodeficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Masur" 1 => "M.A. Michelis" 2 => "G.P. Wormser" 3 => "S.J. Lewin" 4 => "J. Gold" 5 => "M.L. 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