Aplicación de modelos estructurales marginales para estimar los efectos de la terapia antirretroviral en 5 cohortes de seroconvertores al virus de la inmunodeficiencia humana
Marginal structural models application to estimate the effects of antiretroviral therapy in 5 cohorts of HIV seroconverters
Santiago Pérez-Hoyosa,b,
, Inmaculada Ferrerosa,c, Miguel A. Hernánd, GEMES e
Autor para correspondencia
perez_san@gva.es
Correspondencia: Dr. Santiago Pérez-Hoyos. Escuela Valenciana de Estudios en Salud (EVES). Joan de Garay, 21. 46017 Valencia. España.
Correspondencia: Dr. Santiago Pérez-Hoyos. Escuela Valenciana de Estudios en Salud (EVES). Joan de Garay, 21. 46017 Valencia. España.
a Escuela Valenciana de Estudios en Salud (EVES), Valencia, España
b Departament d’Infermeria Comunitaria, Medicina Preventiva i Salut Pública i Història de la Ciencia, Universitat d’Alacant, Alacant, España
c Departamento de Salud Pública, Universidad Miguel Hernández, Alacant, España
d Departamento de Epidemiología, Escuela de Salud Pública, Universidad de Harvard, Boston, Estados Unidos
e Grupo de Estudio Multicéntrico Español de Seroconvertores (ver la relación completa de sus miembros en el anexo)
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Escuela Valenciana de Estudios en Salud (EVES). Joan de Garay, 21. 46017 Valencia. España." ] ] ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Marginal structural models application to estimate the effects of antiretroviral therapy in 5 cohorts of HIV seroconverters" ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2006-02-14" "fechaAceptado" => "2006-10-18" "PalabrasClave" => array:2 [ "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec13987" "palabras" => array:4 [ 0 => "Modelos estructurales marginales" 1 => "Análisis de supervivencia" 2 => "Eficacia de los tratamientos" 3 => "Sida" ] ] ] "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec13988" "palabras" => array:4 [ 0 => "Marginal structural models" 1 => "Survival analysis" 2 => "Treatment efficacy" 3 => "AIDS" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span class="elsevierStyleSectionTitle">Objetivos</span><p class="elsevierStyleSimplePara elsevierViewall">Los métodos convencionales tienen limitaciones para ajustar por factores de confusión dependientes del tiempo para evaluar la efectividad poblacional de tratamientos en estudios observacionales. En este trabajo se muestra un nuevo tipo de metodología, los modelos estructurales marginales (MEM), y se estima la efectividad de la terapia antirretroviral de gran actividad (TARGA) sobre la incidencia de sida o muerte.</p> <span class="elsevierStyleSectionTitle">Sujetos y métodos</span><p class="elsevierStyleSimplePara elsevierViewall">Se identificaron los sujetos sin TARGA seguidos a partir de 1997 en las cohortes de seroconvertores al virus de la inmunodeficiencia humana (VIH) del proyecto GEMES (Grupo de Estudio Multicéntrico Español de Seroconvertores). Para estimar el efecto sobre la incidencia de sida o muerte, se obtuvieron los parámetros de un MEM mediante una regresión logística ponderada por probabilidad inversa. La estimación de los pesos se basó en el recuento de CD4, el tiempo desde la seroconversión, el sexo, la edad, la categoría de trasmisión y el tratamiento previo.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p class="elsevierStyleSimplePara elsevierViewall">Los 917 sujetos elegibles se siguieron durante una media de 3,4 años, durante los cuales se observaron 139 desenlaces de interés. El 42,1% de los participantes recibió TARGA durante el estudio. La tasa relativa fue de 1,01 (intervalo de confianza [IC] del 95%, 0,68-1,49) mediante un modelo de Cox convencional sin covariables, y de 0,90 (IC del 95%, 0,61-1,32) mediante un modelo de Cox convencional con covariables cambiantes en el tiempo. La tasa relativa causal estimada por un MEM fue de 0,74 (IC del 95%, 0,49-1,12).</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p class="elsevierStyleSimplePara elsevierViewall">El efecto beneficioso del TARGA encontrado por los MEM está bien establecido, pero los modelos convencionales no pudieron detectarlo. El uso de un MEM permitió ajustar apropiadamente por la variable CD4, que es a la vez una variable de confusión dependiente del tiempo y está afectada por el uso previo de tratamiento.</p>" ] "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle">Objectives</span><p class="elsevierStyleSimplePara elsevierViewall">Standard methods to evaluate population effectiveness of treatments in observational studies have important limitations to appropriately adjust for time-dependent confounders. In this paper, we describe a recently developed methodological approach, marginal structural models (MSM), and use it to estimate the effectiveness of highly active antiretroviral therapy (HAART) on AIDS or death incidence.</p> <span class="elsevierStyleSectionTitle">Subjects and methods</span><p class="elsevierStyleSimplePara elsevierViewall">We analyzed all subjects followed after 1997 as part of the GEMES project (comprised by several cohorts of HIV seroconverters in Spain) and who had not used HAART before the start of follow-up. To estimate the effect of HAART on AIDS or death incidence, we estimated the parameters of a marginal structural Cox model by fitting an inverse probability weighted logistic regression model. The estimation of the weights was based on CD4 count, time since seroconversion, sex, age, transmission category and previous treatment.</p> <span class="elsevierStyleSectionTitle">Results</span><p class="elsevierStyleSimplePara elsevierViewall">917 eligible subjects were followed for an average of 3.4 years and we observed 139 events. 42.1% of the participants received HAART during the study. The estimated rate ratio was 1.01 (95% confidence interval [CI], 0.68- 1.49) using a Cox model without covariates and 0.90 (95% CI, 0.61-1.32) using a Cox model with time-dependent covariates. The causal rate ratio estimated for MSM was 0.74, (95% CI, 0.49-1.12).</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p class="elsevierStyleSimplePara elsevierViewall">The beneficial effect of HAART estimated by the MSM, but largely missed by conventional methods, is consistent with the findings of previous randomized studies. The MSM appropriately adjusted for the time-dependent covariate CD4 count, which is both a time-varying confounder and is affected by prior treatment.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "Bibliografía" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:21 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.M. Hammer" 1 => "K.E. Squires" 2 => "M.D. Hughes" 3 => "J.M. Grimes" 4 => "L.M. Demeter" 5 => "J.S. Currier" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM199709113371101" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "1997" "volumen" => "337" "paginaInicial" => "725" "paginaFinal" => "733" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9287227" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Randomised placebo-controlled trial of ritonavir in advanced HIV-1 disease. The Advanced HIV Disease Ritonavir Study Group" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.W. Cameron" 1 => "M. Heath-Chiozzi" 2 => "S. Danner" 3 => "C. Cohen" 4 => "S. Kravcik" 5 => "C. Maurath" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "1998" "volumen" => "351" "paginaInicial" => "543" "paginaFinal" => "549" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9492772" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effectiveness of potent antiretroviral therapy on time to AIDS and death in men with known HIV infection duration. Multicenter AIDS Cohort Study Investigators" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Detels" 1 => "A. Muñoz" 2 => "G. McFarlane" 3 => "L.A. Kingsley" 4 => "J.B. Margolick" 5 => "J. Giorgi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "1998" "volumen" => "280" "paginaInicial" => "1497" "paginaFinal" => "1503" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9809730" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effectiveness of highly active antiretroviral therapy in Spanish cohorts of HIV seroconverters: differences by transmission category" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Pérez-Hoyos" 1 => "J. Del Amo" 2 => "R. Muga" 3 => "J. Del Romero" 4 => "O. García" 5 => "R. Guerrero" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.aids.0000050782.28043.77" "Revista" => array:6 [ "tituloSerie" => "AIDS" "fecha" => "2003" "volumen" => "17" "paginaInicial" => "353" "paginaFinal" => "359" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12556689" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Changes over calendar time in the risk of specific first AIDS-defining events following HIV seroconversion, adjusting for competing risks" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Babiker" 1 => "J. Darbyshire" 2 => "P. Pezzotti" 3 => "K. Porter" 4 => "G. Rezza" 5 => "S.A. Walker" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Int J Epidemiol" "fecha" => "2002" "volumen" => "31" "paginaInicial" => "951" "paginaFinal" => "958" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12435766" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib6" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Determinants of survival following HIV-1 seroconversion after the introduction of HAART" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Porter" 1 => "A. Babiker" 2 => "K. Bhaskaran" 3 => "J. Darbyshire" 4 => "P. Pezzotti" 5 => "A.S. Walker" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2003" "volumen" => "362" "paginaInicial" => "1267" "paginaFinal" => "1274" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14575971" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib7" "etiqueta" => "7." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.A. Hernan" 1 => "B. Brumback" 2 => "J.M. Robins" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Epidemiology" "fecha" => "2000" "volumen" => "11" "paginaInicial" => "561" "paginaFinal" => "570" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10955409" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib8" "etiqueta" => "8." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Marginal structural models and causal inference in epidemiology" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.M. Robins" 1 => "M.A. Hernan" 2 => "B. Brumback" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Epidemiology" "fecha" => "2000" "volumen" => "11" "paginaInicial" => "550" "paginaFinal" => "560" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10955408" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib9" "etiqueta" => "9." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of highly active antiretroviral therapy on time to acquired immunodeficiency syndrome or death using marginal structural models" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.R. Cole" 1 => "M.A. Hernan" 2 => "J.M. Robins" 3 => "K. Anastos" 4 => "J. Chmiel" 5 => "R. Detels" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Epidemiol" "fecha" => "2003" "volumen" => "158" "paginaInicial" => "687" "paginaFinal" => "694" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14507605" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib10" "etiqueta" => "10." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term effectiveness of potent antiretroviral therapy in preventing AIDS and death: a prospective cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.A. Sterne" 1 => "M.A. Hernan" 2 => "B. Ledergerber" 3 => "K. Tilling" 4 => "R. Weber" 5 => "P. Sendi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(05)67022-5" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2005" "volumen" => "366" "paginaInicial" => "378" "paginaFinal" => "384" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16054937" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib11" "etiqueta" => "11." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "El período de incubación del sida en España antes de la terapia antirretroviral de alta eficacia" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "GEMES (Grupo Español Multicéntrico para el Estudio de Seroconversores)" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Med Clin (Barc)" "fecha" => "2000" "volumen" => "115" "paginaInicial" => "681" "paginaFinal" => "686" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib12" "etiqueta" => "12." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "On the application of probability theory to agricultural experiments: essay on principles, section 9" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J. Neyman" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Statistical Science" "fecha" => "1990" "volumen" => "5" "paginaInicial" => "465" "paginaFinal" => "480" ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib13" "etiqueta" => "13." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A definition of causal effect for epidemiological research" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.A. Hernan" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Epidemiol Community Health" "fecha" => "2004" "volumen" => "58" "paginaInicial" => "265" "paginaFinal" => "271" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15026432" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib14" "etiqueta" => "14." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A generalization of sampling without replacement from a finite population" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D.G. Horvitz" 1 => "D.J. Thompson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "JASA" "fecha" => "1952" "volumen" => "47" "paginaInicial" => "663" "paginaFinal" => "685" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib15" "etiqueta" => "15." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Estimating causal effects from epidemiological data. J Epidemiol" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.A. Hernan" 1 => "J.M. Robins" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Community Health" "fecha" => "2006" "volumen" => "60" "paginaInicial" => "578" "paginaFinal" => "586" ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib16" "etiqueta" => "16." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A structural approach to selection bias" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.A. Hernan" 1 => "S. Hernández-Díaz" 2 => "J.M. Robins" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Epidemiology" "fecha" => "2004" "volumen" => "15" "paginaInicial" => "615" "paginaFinal" => "625" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15308962" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib17" "etiqueta" => "17." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Marginal structural models. Proceedings or the American Statistical Association, Section on Bayesian Statistical Science" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "JM. Robins" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "1998" "editorial" => "American Statistical Association" "editorialLocalizacion" => "Alexandria" ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib18" "etiqueta" => "18." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Marginal structural models to estimate of joint causal effect of non-randomized treatments" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.A. Hernan" 1 => "B. Brumback" 2 => "J.M. Robins" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "JASA" "fecha" => "2001" "volumen" => "96" "paginaInicial" => "440" "paginaFinal" => "448" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib19" "etiqueta" => "19." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Controlling for time-dependent confounding using marginal structural models" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Z. Fewell" 1 => "M.A. Hernan" 2 => "F. Wolfe" 3 => "K. Tilling" 4 => "H. Choi" 5 => "J.A. Sterne" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Stata J" "fecha" => "2004" "volumen" => "4" "paginaInicial" => "402" "paginaFinal" => "420" ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib20" "etiqueta" => "20." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fallibility in estimating direct effects" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S.R. Cole" 1 => "M.A. Hernan" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Int J Epidemiol" "fecha" => "2002" "volumen" => "31" "paginaInicial" => "163" "paginaFinal" => "165" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11914314" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib21" "etiqueta" => "21." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Selection by indication of potent antiretroviral therapy use in a large cohort of women infected with human immunodeficiency virus" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Ahdieh" 1 => "S.J. Gange" 2 => "R. Greenblatt" 3 => "H. Minkoff" 4 => "K. Anastos" 5 => "M. Young" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Epidemiol" "fecha" => "2000" "volumen" => "152" "paginaInicial" => "923" "paginaFinal" => "933" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11092434" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "es" "url" => "/02139111/0000002100000001/v2_201301241555/S021391110771974X/v2_201301241555/es/main.assets" "Apartado" => array:4 [ "identificador" => "636" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Nota Metodológica" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/02139111/0000002100000001/v2_201301241555/S021391110771974X/v2_201301241555/es/main.pdf?idApp=WGSE&text.app=https://gacetasanitaria.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S021391110771974X?idApp=WGSE" ]
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