array:23 [
  "pii" => "S1695403300773929"
  "issn" => "16954033"
  "doi" => "10.1016/S1695-4033(00)77392-9"
  "estado" => "S300"
  "fechaPublicacion" => "2000-06-01"
  "aid" => "77392"
  "copyright" => "Asociación Española de Pediatría"
  "copyrightAnyo" => "2000"
  "documento" => "article"
  "crossmark" => 0
  "subdocumento" => "fla"
  "cita" => "An Pediatr (Barc). 2000;52:501-6"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:2 [
    "total" => 1544
    "formatos" => array:3 [
      "EPUB" => 86
      "HTML" => 960
      "PDF" => 498
    ]
  ]
  "itemSiguiente" => array:18 [
    "pii" => "S1695403300773930"
    "issn" => "16954033"
    "doi" => "10.1016/S1695-4033(00)77393-0"
    "estado" => "S300"
    "fechaPublicacion" => "2000-06-01"
    "aid" => "77393"
    "copyright" => "Asociación Española de Pediatría"
    "documento" => "article"
    "crossmark" => 0
    "subdocumento" => "fla"
    "cita" => "An Pediatr (Barc). 2000;52:507-15"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 2583
      "formatos" => array:3 [
        "EPUB" => 87
        "HTML" => 2036
        "PDF" => 460
      ]
    ]
    "es" => array:10 [
      "idiomaDefecto" => true
      "titulo" => "Densidad mineral ósea en la diabetes mellitus infantojuvenil"
      "tienePdf" => "es"
      "tieneTextoCompleto" => 0
      "tieneResumen" => array:2 [
        0 => "es"
        1 => "en"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "507"
          "paginaFinal" => "515"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "en" => array:1 [
          "titulo" => "Bone mineral density in type 1 diabetes mellitus"
        ]
      ]
      "contieneResumen" => array:2 [
        "es" => true
        "en" => true
      ]
      "contienePdf" => array:1 [
        "es" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "E. Viña Simón, G. Bueno Lozano, M.I. Armada Maresca, J.L. Ruibal Francisco, C. Fernández Pérez, C. Lozano Tonkin, E. Casado de Frías"
          "autores" => array:7 [
            0 => array:2 [
              "nombre" => "E."
              "apellidos" => "Viña Simón"
            ]
            1 => array:2 [
              "nombre" => "G."
              "apellidos" => "Bueno Lozano"
            ]
            2 => array:2 [
              "nombre" => "M.I."
              "apellidos" => "Armada Maresca"
            ]
            3 => array:2 [
              "nombre" => "J.L."
              "apellidos" => "Ruibal Francisco"
            ]
            4 => array:2 [
              "nombre" => "C."
              "apellidos" => "Fernández Pérez"
            ]
            5 => array:2 [
              "nombre" => "C."
              "apellidos" => "Lozano Tonkin"
            ]
            6 => array:2 [
              "nombre" => "E."
              "apellidos" => "Casado de Frías"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "es"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1695403300773930?idApp=UINPBA00005H"
    "url" => "/16954033/0000005200000006/v1_201307051505/S1695403300773930/v1_201307051505/es/main.assets"
  ]
  "itemAnterior" => array:18 [
    "pii" => "S1695403300773917"
    "issn" => "16954033"
    "doi" => "10.1016/S1695-4033(00)77391-7"
    "estado" => "S300"
    "fechaPublicacion" => "2000-06-01"
    "aid" => "77391"
    "copyright" => "Asociación Española de Pediatría"
    "documento" => "article"
    "crossmark" => 0
    "subdocumento" => "edi"
    "cita" => "An Pediatr (Barc). 2000;52:497-500"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 3084
      "formatos" => array:3 [
        "EPUB" => 57
        "HTML" => 2616
        "PDF" => 411
      ]
    ]
    "es" => array:7 [
      "idiomaDefecto" => true
      "titulo" => "Pediatría basada en la evidencia"
      "tienePdf" => "es"
      "tieneTextoCompleto" => 0
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "497"
          "paginaFinal" => "500"
        ]
      ]
      "contienePdf" => array:1 [
        "es" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "A.E. Curley, H.L. Halliday"
          "autores" => array:2 [
            0 => array:2 [
              "nombre" => "A.E."
              "apellidos" => "Curley"
            ]
            1 => array:2 [
              "nombre" => "H.L."
              "apellidos" => "Halliday"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "es"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1695403300773917?idApp=UINPBA00005H"
    "url" => "/16954033/0000005200000006/v1_201307051505/S1695403300773917/v1_201307051505/es/main.assets"
  ]
  "es" => array:14 [
    "idiomaDefecto" => true
    "titulo" => "Correlación entre carga viral elevada y concentraciones de TNF-α y cICAM-1 en el plasma de niños infectados por el VIH-1"
    "tieneTextoCompleto" => 0
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "501"
        "paginaFinal" => "506"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "S. Resino, J.L. Jiménez, J.M. Bellón, D. Gurbindo, M.A. Muñoz-Fernández"
        "autores" => array:5 [
          0 => array:3 [
            "nombre" => "S."
            "apellidos" => "Resino"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "J&#46;L&#46;"
            "apellidos" => "Jim&#233;nez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "J&#46;M&#46;"
            "apellidos" => "Bell&#243;n"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "D&#46;"
            "apellidos" => "Gurbindo"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          4 => array:4 [
            "nombre" => "M&#46;A&#46;"
            "apellidos" => "Mu&#241;oz-Fern&#225;ndez"
            "email" => array:1 [
              0 => "Mmunoz&#64;cbm&#46;uam&#46;es"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:2 [
          0 => array:3 [
            "entidad" => "Secciones de Inmunolog&#237;a Hospital General Universitario Gregorio Mara&#241;&#243;n&#46; Madrid&#46;"
            "etiqueta" => "<span class="elsevierStyleSup">a</span>"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Inmuno-Pediatr&#237;a&#46; Hospital General Universitario Gregorio Mara&#241;&#243;n&#46; Madrid&#46;"
            "etiqueta" => "<span class="elsevierStyleSup">b</span>"
            "identificador" => "aff0010"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#42;"
            "correspondencia" => "Correspondencia&#58; Hospital General Universitario Gregorio Mara&#241;&#243;n&#46; Divisi&#243;n de Inmunolog&#237;a&#46; Dr&#46; Esquerdo&#44; 46&#46; 28007 Madrid"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "en" => array:1 [
        "titulo" => "Relationship between high plasma viral load and levels of tnf-a and cicam-1 in vertically hiv-1 infected children"
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2000-02-29"
    "fechaAceptado" => "2000-04-30"
    "PalabrasClave" => array:2 [
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec186374"
          "palabras" => array:5 [
            0 => "VIH"
            1 => "Ni&#241;os"
            2 => "Carga viral"
            3 => "TNF-&#945;"
            4 => "cICAM-1"
          ]
        ]
      ]
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Key words"
          "identificador" => "xpalclavsec186373"
          "palabras" => array:5 [
            0 => "HIV"
            1 => "Children"
            2 => "Viral load"
            3 => "TNF-a"
            4 => "cICAM-1"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "es" => array:1 [
        "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Analizar si existe relaci&#243;n entre los valores plasm&#225;ticos del factor de necrosis tumoral &#40;TNF-&#945;&#41; y la mol&#233;cula de adhesi&#243;n intercelular circulante tipo 1 &#40;cICAM-1&#41; con valores de carga viral plasm&#225;tica &#40;CV&#41; en ni&#241;os infectados verticalmente por el VIH&#46;</p> <span class="elsevierStyleSectionTitle">Pacientes y m&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Estudiamos 44 ni&#241;os VIH-1 y un grupo control de 38 ni&#241;os no infectados por el VIH-1&#46; Las subpoblaciones celulares se realizaron por citometr&#237;a de flujo&#44; las concentraciones de TNF-&#945; y cICAM-1 se cuantificaron por t&#233;cnicas de enzimoinmunoan&#225;lisis y la CV se cuantific&#243; mediante un an&#225;lisis molecular est&#225;ndar comercial&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Los ni&#241;os infectados por el VIH-1 presentaron valores significativamente m&#225;s altos de TNF-&#945; y cICAM-1 que los ni&#241;os del grupo control&#46; Dividimos a los ni&#241;os VIH-1 seg&#250;n los valores de CV&#46; Los ni&#241;os VIH-1 con CV mayor de 50&#46;000 copias&#47;ml produjeron m&#225;s TNF-&#945; &#40;12&#44;83&#59; IC del 95&#37;&#58; 24&#44;71-0&#44;95 pg&#47;ml&#41; y cICAM-1 &#40;248&#44;94&#59; IC del 95&#37;&#58; 419&#44;01-78&#44;84 ng&#47;ml&#41; que los ni&#241;os VIH-1 con CV inferior a 50&#46;000 copias&#47;ml&#44; de tal forma que se produc&#237;a un incremento de 6&#44;57 pg&#47;ml de TNF-&#945; y de 119&#44;97 ng&#47;ml de cICAM-1 por cada log10 de CV&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Nuestros datos indican que a medida que en el plasma de los ni&#241;os VIH-1 se incrementan los valores de CV tambi&#233;n se incrementan los valores de TNF-&#945; y cICAM-1&#46;</p>"
      ]
      "en" => array:1 [
        "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">To assess the relationship among plasma TNF-&#945; and cICAM-1 levels and plasma viral load &#40;VL&#41; in HIV-infected children and to compare these values with those of healthy non-HIV infected children&#46;</p> <span class="elsevierStyleSectionTitle">Patients and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">We studied 44 HIV-infected children and 38 non-HIV-infected children&#46; The VL was quantified using standard molecular assay&#46; CD4 and CD8 lymphocyte subpopulations were determined by flow cytometry&#46; TNF-&#945; and cICAM-1 were quantified using commercially available specific enzyme-linked immunosorbent assay &#40;ELISA&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Levels of TNF-&#945; and cICAM-1 were higher in HIV-infect-ed children than in non-HIV infected children&#46; HIV-infected children with VL &#62; 50000 copies&#47;ml had higher levels of TNF-&#945; &#40;12&#46;83&#59; 95&#37; CI&#58; 24&#46;71 to 0&#46;95 pg&#47;ml&#41; and cICAM-1 &#40;248&#46;94&#59; 95&#37; CI&#58; 419&#46;01 to 78&#46;84 ng&#47;ml&#41; than HIV-infected children with VL &#60; 50000 copies&#47;ml&#46; Interestingly&#44; we found an increase of 6&#46;57 pg&#47;ml of TNF-&#945; and 119&#46;97 ng&#47;ml of cICAM-1 levels for each log10 of VL&#46;</p> <span class="elsevierStyleSectionTitle">conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">HIV-infected children had higher levels of TNF-&#945; and cICAM-1 than healthy controls&#46; Our data indicate a positive correlation among plasma TNF-a and cICAM-1 and VL levels&#46;</p>"
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Bibliograf&#237;a"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:33 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Pantaleo"
                            1 => "C&#46; Graziosi"
                            2 => "J&#46;F&#46; Demarest"
                            3 => "L&#46; Butini"
                            4 => "M&#46; Montroni"
                            5 => "C&#46;H&#46; Fox"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/362355a0"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nature"
                        "fecha" => "1993"
                        "volumen" => "362"
                        "paginaInicial" => "355"
                        "paginaFinal" => "358"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8455722"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Detection of three distinct patterns of T helper cell dysfunction in asymptomatic&#44; human immunodeficiency virusseropositive&#46; Independence of CD4&#43; cell numbers and clinical stating"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Clerici"
                            1 => "N&#46;I&#46; Stocks"
                            2 => "R&#46;A&#46; Zajac"
                            3 => "R&#46;N&#46; Boswell"
                            4 => "D&#46;R&#46; Lucey"
                            5 => "C&#46;S&#46; Via"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI114376"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "1989"
                        "volumen" => "84"
                        "paginaInicial" => "1892"
                        "paginaFinal" => "1899"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2574188"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Elevated CD38 antigen expression on CD8&#43; T cells is a stronger marker for the risk of chronic HIV disease progression to AIDS and death in the Multicenter AIDS Cohort Study than CD4&#43; cell count&#44; soluble immune activation markers&#44; or combinations of HLA-DR and CD38 expression"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "Z&#46; Liu"
                            1 => "W&#46;G&#46; Cumberland"
                            2 => "L&#46;E&#46; Hultin"
                            3 => "H&#46;E&#46; Prince"
                            4 => "R&#46; Detels"
                            5 => "J&#46;V&#46; Giorgi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Acquir Immune Defic Syndr Hum Retrovirol"
                        "fecha" => "1997"
                        "volumen" => "16"
                        "paginaInicial" => "83"
                        "paginaFinal" => "92"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9358102"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Serum level of tumor necrosis factor-alpha &#40;TNF alpha&#41; and soluble TNF receptors in human immunodeficiency virus type 1 infection-correlations to clinical&#44; immunologic&#44; and virologic parameters"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "P&#46; Aukrust"
                            1 => "N&#46;B&#46; Liabakk"
                            2 => "F&#46; Muller"
                            3 => "E&#46; Lien"
                            4 => "T&#46; Espevik"
                            5 => "S&#46;S&#46; Froland"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Infect Dis"
                        "fecha" => "1994"
                        "volumen" => "169"
                        "paginaInicial" => "420"
                        "paginaFinal" => "424"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7906293"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Phenotypic and functional separation of memory and effector human CD8&#43; T cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Hamann"
                            1 => "P&#46;A&#46; Baars"
                            2 => "M&#46;H&#46; Rep"
                            3 => "B&#46; Hooibrink"
                            4 => "S&#46;R&#46; Kerkhof-Garde"
                            5 => "M&#46;R&#46; Klein"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Exp Med"
                        "fecha" => "1997"
                        "volumen" => "186"
                        "paginaInicial" => "1407"
                        "paginaFinal" => "1418"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9348298"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tumor necrosis factor production in HIV-seropositive subjects&#46; Relationships with lung opportunistic infections and HIV expression in alveolar macrophages"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "D&#46; Israel-Biet"
                            1 => "J&#46; Cadranel"
                            2 => "K&#46; Beldjord"
                            3 => "J&#46;M&#46; Andrieu"
                            4 => "A&#46; Jeffrey"
                            5 => "P&#46; Even"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "1991"
                        "volumen" => "147"
                        "paginaInicial" => "490"
                        "paginaFinal" => "497"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1906500"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The role of interferon and tumor necrosis factor in the pathogenesis of AIDS"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46;S&#46; Lau"
                            1 => "B&#46;R&#46; Williams"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Exp Pathol"
                        "fecha" => "1990"
                        "volumen" => "5"
                        "paginaInicial" => "111"
                        "paginaFinal" => "122"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1709966"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Relationship of plasma HIVRNA levels and levels of TNF-alpha and immune activation products in HIVinfection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;F&#46; Salazar-Gonz&#225;lez"
                            1 => "O&#46; Mart&#237;nez-Maza"
                            2 => "N&#46; Aziz"
                            3 => "J&#46;A&#46; Kolberg"
                            4 => "T&#46; Yeghiazarian"
                            5 => "L&#46;P&#46; Shen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Immunol Immunopathol"
                        "fecha" => "1997"
                        "volumen" => "84"
                        "paginaInicial" => "36"
                        "paginaFinal" => "45"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9191882"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cytokine pattern in relation to disease progression in human immunodeficiency virus-infected children"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Than"
                            1 => "R&#46; Hu"
                            2 => "N&#46; Oyaizu"
                            3 => "J&#46; Romano"
                            4 => "X&#46; Wang"
                            5 => "S&#46; Sheikh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Infect Dis"
                        "fecha" => "1997"
                        "volumen" => "175"
                        "paginaInicial" => "47"
                        "paginaFinal" => "56"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8985195"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Elevated leels of circulating intercellular adhesion molecule 1 and tumor necrosis factor a in the serum of children vertically infection with HIV-1&#46; Pediatric AIDS and HIV Infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "E&#46; Obreg&#243;n"
                            1 => "C&#46; B&#246;rner"
                            2 => "J&#46; Navarro"
                            3 => "M&#46;D&#46; Gurbindo"
                            4 => "E&#46; Fern&#225;ndez-Cruz"
                            5 => "M&#46;A&#46; Mu&#241;oz-Fern&#225;ndez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Fetus and adolescent"
                        "fecha" => "1996"
                        "volumen" => "7"
                        "paginaInicial" => "413"
                        "paginaFinal" => "417"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Elevated levels of tumor necrosis factor-alpha in Zairian neonate plasmas&#58; implications for perinatal infection with the human immunodeficiency virus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46;C&#46; Brown"
                            1 => "G&#46; Poli"
                            2 => "N&#46; Lubaki"
                            3 => "M&#46; St&#46; Louis"
                            4 => "F&#46; Davachi"
                            5 => "L&#46; Musey"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Infect Dis"
                        "fecha" => "1994"
                        "volumen" => "169"
                        "paginaInicial" => "975"
                        "paginaFinal" => "980"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8169428"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tumor necrosis factor alpha activates human immunodeficiency virus type 1 throughinduction of nuclear factor binding to the NF-kappa B sites in the long terminal repeat"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "E&#46;J&#46; Duh"
                            1 => "W&#46;J&#46; Maury"
                            2 => "T&#46;M&#46; Folks"
                            3 => "A&#46;S&#46; Fauci"
                            4 => "A&#46;B&#46; Rabson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Obstet Gynecol"
                        "fecha" => "1989"
                        "volumen" => "161"
                        "paginaInicial" => "501"
                        "paginaFinal" => "502"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2764068"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Replication of human immunodeficiency virus-1 in primary human T cells is dependent on the autocrine secretion of tumor necrosis factor through the control of nuclear factor-kappa B activation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46;A&#46; Mu&#241;oz-Fern&#225;ndez"
                            1 => "J&#46; Navarro"
                            2 => "A&#46; Garc&#237;a"
                            3 => "C&#46; Punz&#243;n"
                            4 => "E&#46; Fern&#225;ndez-Cruz"
                            5 => "M&#46; Fresno"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "1997"
                        "volumen" => "100"
                        "paginaInicial" => "838"
                        "paginaFinal" => "845"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9438495"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tumour necrosis factors &#40;alpha&#44; beta&#41; induced by HIV-1 in peripheral blood mononuclear cells potentiate virus replication"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46; Vyakarman"
                            1 => "J&#46; McKeating"
                            2 => "A&#46; Meager"
                            3 => "P&#46;C&#46; Beverley"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Aids"
                        "fecha" => "1990"
                        "volumen" => "4"
                        "paginaInicial" => "21"
                        "paginaFinal" => "27"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1969279"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Endothelial-leukocyte adhesion molecules"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "M&#46;P&#46; Bevilacqua"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1146/annurev.iy.11.040193.004003"
                      "Revista" => array:6 [
                        "tituloSerie" => "Annu Rev Immunol"
                        "fecha" => "1993"
                        "volumen" => "11"
                        "paginaInicial" => "767"
                        "paginaFinal" => "804"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8476577"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biologic basis for interleukin-1 in disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "C&#46;A&#46; Dinarello"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Blood"
                        "fecha" => "1996"
                        "volumen" => "87"
                        "paginaInicial" => "2096"
                        "paginaFinal" => "2147"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Elevated serum levels of circulating intercellular adhesion molecule-1 in HIV infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "F&#46; Puppo"
                            1 => "S&#46; Brenci"
                            2 => "M&#46; Scudeletti"
                            3 => "L&#46; Lanza"
                            4 => "O&#46; Bosco"
                            5 => "F&#46; Indiveri"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Aids"
                        "fecha" => "1993"
                        "volumen" => "7"
                        "paginaInicial" => "593"
                        "paginaFinal" => "594"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8099491"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Elevated concentrations of circulating intercellular adhesion molecule 1 &#40;ICAM-1&#41; inHIV-1 infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Most"
                            1 => "R&#46; Zangerle"
                            2 => "M&#46; Herold"
                            3 => "D&#46; Fuchs"
                            4 => "H&#46; Wachter"
                            5 => "P&#46; Fritsch"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Acquir Immune Defic Syndr"
                        "fecha" => "1993"
                        "volumen" => "6"
                        "paginaInicial" => "221"
                        "paginaFinal" => "226"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8095541"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Detection of circulating intercellular adhesion molecule-1 antigen in malignant diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Tsujisaki"
                            1 => "K&#46; Imai"
                            2 => "H&#46; Hirata"
                            3 => "Y&#46; Hanzawa"
                            4 => "J&#46; Masuya"
                            5 => "T&#46; Nakano"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Immunol"
                        "fecha" => "1991"
                        "volumen" => "85"
                        "paginaInicial" => "3"
                        "paginaFinal" => "8"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1712683"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Relationship of virologic&#44; immunologic and clinical parameters in infants with vertically acquired humanimmunodeficiency virus type 1 infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46;A&#46; Mu&#241;oz-Fern&#225;ndez"
                            1 => "E&#46; Obreg&#243;n"
                            2 => "J&#46; Navarro"
                            3 => "C&#46; Borner"
                            4 => "M&#46;D&#46; Gurbindo"
                            5 => "T&#46;H&#46; Sampelayo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1203/00006450-199610000-00014"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Res"
                        "fecha" => "1996"
                        "volumen" => "40"
                        "paginaInicial" => "597"
                        "paginaFinal" => "602"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8888289"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Center for Diseases Control Prevention&#46; Revised classification systemfor HIV-1 infection in children less than 13 years of age"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "CDCP&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Mmwr"
                        "fecha" => "1994"
                        "volumen" => "43"
                        "paginaInicial" => "1"
                        "paginaFinal" => "13"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7969014"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Marcadores predictivos de supervivencia en ni&#241;os menores de 12 meses de edad infectados verticalmente por el virus de la inmunodeficiencia humana"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S&#46; Resino"
                            1 => "J&#46;L&#46; Jim&#233;nez"
                            2 => "D&#46; Gurbindo"
                            3 => "M&#46;A&#46; Mu&#241;oz-Fern&#225;ndez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Med Clin &#40;Barc&#41;"
                        "fecha" => "1999"
                        "volumen" => "113"
                        "paginaInicial" => "561"
                        "paginaFinal" => "566"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tumor necrosis factor alpha functions in an autocrine manner in the induction of human immunodeficiency virus expression"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Poli"
                            1 => "A&#46; Kinter"
                            2 => "J&#46;S&#46; Justement"
                            3 => "J&#46;H&#46; Kehrl"
                            4 => "P&#46; Bressler"
                            5 => "S&#46; Stanley"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Proc Natl Acad Sci USA"
                        "fecha" => "1990"
                        "volumen" => "87"
                        "paginaInicial" => "782"
                        "paginaFinal" => "795"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2300561"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "HIV-1 induces tumour necrosis factor and IL-1 gene expression in-primary human macrophages independent of productive infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "G&#46; Herbein"
                            1 => "S&#46; Keshav"
                            2 => "M&#46; Collin"
                            3 => "L&#46;J&#46; Montaner"
                            4 => "S&#46; Gordon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Immunol"
                        "fecha" => "1994"
                        "volumen" => "95"
                        "paginaInicial" => "442"
                        "paginaFinal" => "449"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7511077"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Dysregulation of membrane-bound tumor necrosis factor-alpha and tumor necrosis factor receptors on mononuclear cells in human immunodeficiency virus type 1 infection&#58; low percentage of p75-tumor necrosis factor receptor positive cells in patients with advanced disease and high viral load"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46; Hestdal"
                            1 => "P&#46; Aukrust"
                            2 => "F&#46; Muller"
                            3 => "E&#46; Lien"
                            4 => "V&#46; Bjerkeli"
                            5 => "T&#46; Espevik"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Pediatr Infec Dis J"
                        "fecha" => "1997"
                        "volumen" => "16"
                        "paginaInicial" => "963"
                        "paginaFinal" => "967"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reduced concentrations of HIV-RNA and TNF-alpha coexist in CSF of AIDS patients with progressive multifocal leukoencephalopathy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "L&#46; Monno"
                            1 => "G&#46;B&#46; Zimatore"
                            2 => "M&#46; Di Stefano"
                            3 => "A&#46; Appice"
                            4 => "P&#46; Livrea"
                            5 => "G&#46; Angarano"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Neurol Neurosurg Psychiatry"
                        "fecha" => "1999"
                        "volumen" => "67"
                        "paginaInicial" => "369"
                        "paginaFinal" => "373"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10449561"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The relationship between serum human immunodeficiency virus type 1 &#40;HIV-1&#41; RNA level&#44; CD4 lymphocyte percent&#44; and long-term mortality risk in HIV-1-infected children&#46; National Institute of Child Health and Human Development IntravenousImmunoglobulinClinical Trial Study Group"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46;M&#46; Mofenson"
                            1 => "J&#46; Korelitz"
                            2 => "W&#46;A&#46; Meyer 3rd"
                            3 => "J&#46; Bethel"
                            4 => "K&#46; Rich"
                            5 => "S&#46; Pahwa"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Infect Dis"
                        "fecha" => "1997"
                        "volumen" => "175"
                        "paginaInicial" => "1029"
                        "paginaFinal" => "1038"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9129063"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Predictive markers of clinical outcome in vertically HIV-1 infected infants&#44; a prospective longitudinal study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "S&#46; Resino"
                            1 => "M&#46;D&#46; Gurbindo"
                            2 => "J&#46;M&#46; Bell&#243;n"
                            3 => "S&#46; S&#225;nchez-Ram&#243;n"
                            4 => "M&#46;A&#46; Mu&#241;oz-Fern&#225;ndez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Pediatr Res"
                        "fecha" => "2000"
                        "volumen" => "47"
                        "paginaInicial" => "1"
                        "paginaFinal" => "7"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Role of cytokines in the pathogenesis of human immunodeficiency virus infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "G&#46; Poli"
                            1 => "A&#46; Fauci"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:4 [
                        "titulo" => "Human cytokines&#58; their role in disease and therapy"
                        "paginaInicial" => "421"
                        "paginaFinal" => "449"
                        "serieFecha" => "1995"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cytokines and HIV infection&#58; is Aids a tumor necrosis factor disease&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "T&#46; Matsuyama"
                            1 => "N&#46; Kobayashi"
                            2 => "N&#46; Yamamoto"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Aids"
                        "fecha" => "1991"
                        "volumen" => "5"
                        "paginaInicial" => "1405"
                        "paginaFinal" => "1417"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1814326"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Resino S&#44; Mu&#241;oz-Fern&#225;ndez MA&#46; Marcadores predictivos de evoluci&#243;n de la infecci&#243;n pedi&#225;trica por el virus de la inmunodeficiencia humana tipo 1&#46; Acta Pediatr Esp 2000 &#40;en prensa&#41;&#46;"
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anti-tumor necrosis factor-alpha therapy of rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Feldmann"
                            1 => "M&#46;J&#46; Elliott"
                            2 => "J&#46;N&#46; Woody"
                            3 => "R&#46;N&#46; Maini"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Adv Immunol"
                        "fecha" => "1997"
                        "volumen" => "64"
                        "paginaInicial" => "283"
                        "paginaFinal" => "350"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9100984"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Characterization of intercellular adhesion molecule-1 ectodomain &#40;sICAM-1&#41; as an inhibitor of lymphocyte function-associated molecule-1 interaction with ICAM-1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "D&#46;M&#46; Meyer"
                            1 => "M&#46;L&#46; Dustin"
                            2 => "C&#46;P&#46; Carron"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "1995"
                        "volumen" => "155"
                        "paginaInicial" => "3578"
                        "paginaFinal" => "3584"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7561056"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "es"
  "url" => "/16954033/0000005200000006/v1_201307051505/S1695403300773929/v1_201307051505/es/main.assets"
  "Apartado" => array:4 [
    "identificador" => "14282"
    "tipo" => "SECCION"
    "es" => array:2 [
      "titulo" => "Originales"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "es"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/16954033/0000005200000006/v1_201307051505/S1695403300773929/v1_201307051505/es/main.pdf?idApp=UINPBA00005H&text.app=https://analesdepediatria.org/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1695403300773929?idApp=UINPBA00005H"
]
Compartir
Información de la revista
Vol. 52. Núm. 6.
Páginas 501-506 (junio 2000)
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Vol. 52. Núm. 6.
Páginas 501-506 (junio 2000)
Acceso a texto completo
Correlación entre carga viral elevada y concentraciones de TNF-α y cICAM-1 en el plasma de niños infectados por el VIH-1
Relationship between high plasma viral load and levels of tnf-a and cicam-1 in vertically hiv-1 infected children
Visitas
6373
S. Resinoa, J.L. Jiméneza, J.M. Bellóna, D. Gurbindob, M.A. Muñoz-Fernándeza,
Autor para correspondencia
Mmunoz@cbm.uam.es

Correspondencia: Hospital General Universitario Gregorio Marañón. División de Inmunología. Dr. Esquerdo, 46. 28007 Madrid
a Secciones de Inmunología Hospital General Universitario Gregorio Marañón. Madrid.
b Inmuno-Pediatría. Hospital General Universitario Gregorio Marañón. Madrid.
Este artículo ha recibido
Información del artículo
Objetivo

Analizar si existe relación entre los valores plasmáticos del factor de necrosis tumoral (TNF-α) y la molécula de adhesión intercelular circulante tipo 1 (cICAM-1) con valores de carga viral plasmática (CV) en niños infectados verticalmente por el VIH.

Pacientes y métodos

Estudiamos 44 niños VIH-1 y un grupo control de 38 niños no infectados por el VIH-1. Las subpoblaciones celulares se realizaron por citometría de flujo, las concentraciones de TNF-α y cICAM-1 se cuantificaron por técnicas de enzimoinmunoanálisis y la CV se cuantificó mediante un análisis molecular estándar comercial.

Resultados

Los niños infectados por el VIH-1 presentaron valores significativamente más altos de TNF-α y cICAM-1 que los niños del grupo control. Dividimos a los niños VIH-1 según los valores de CV. Los niños VIH-1 con CV mayor de 50.000 copias/ml produjeron más TNF-α (12,83; IC del 95%: 24,71-0,95 pg/ml) y cICAM-1 (248,94; IC del 95%: 419,01-78,84 ng/ml) que los niños VIH-1 con CV inferior a 50.000 copias/ml, de tal forma que se producía un incremento de 6,57 pg/ml de TNF-α y de 119,97 ng/ml de cICAM-1 por cada log10 de CV.

Conclusiones

Nuestros datos indican que a medida que en el plasma de los niños VIH-1 se incrementan los valores de CV también se incrementan los valores de TNF-α y cICAM-1.

Palabras clave:
VIH
Niños
Carga viral
TNF-α
cICAM-1
Objective

To assess the relationship among plasma TNF-α and cICAM-1 levels and plasma viral load (VL) in HIV-infected children and to compare these values with those of healthy non-HIV infected children.

Patients and methods

We studied 44 HIV-infected children and 38 non-HIV-infected children. The VL was quantified using standard molecular assay. CD4 and CD8 lymphocyte subpopulations were determined by flow cytometry. TNF-α and cICAM-1 were quantified using commercially available specific enzyme-linked immunosorbent assay (ELISA).

Results

Levels of TNF-α and cICAM-1 were higher in HIV-infect-ed children than in non-HIV infected children. HIV-infected children with VL > 50000 copies/ml had higher levels of TNF-α (12.83; 95% CI: 24.71 to 0.95 pg/ml) and cICAM-1 (248.94; 95% CI: 419.01 to 78.84 ng/ml) than HIV-infected children with VL < 50000 copies/ml. Interestingly, we found an increase of 6.57 pg/ml of TNF-α and 119.97 ng/ml of cICAM-1 levels for each log10 of VL.

conclusions

HIV-infected children had higher levels of TNF-α and cICAM-1 than healthy controls. Our data indicate a positive correlation among plasma TNF-a and cICAM-1 and VL levels.

Key words:
HIV
Children
Viral load
TNF-a
cICAM-1
El Texto completo está disponible en PDF
Bibliografía
[1.]
G. Pantaleo, C. Graziosi, J.F. Demarest, L. Butini, M. Montroni, C.H. Fox, et al.
HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease.
Nature, 362 (1993), pp. 355-358
[2.]
M. Clerici, N.I. Stocks, R.A. Zajac, R.N. Boswell, D.R. Lucey, C.S. Via, et al.
Detection of three distinct patterns of T helper cell dysfunction in asymptomatic, human immunodeficiency virusseropositive. Independence of CD4+ cell numbers and clinical stating.
J Clin Invest, 84 (1989), pp. 1892-1899
[3.]
Z. Liu, W.G. Cumberland, L.E. Hultin, H.E. Prince, R. Detels, J.V. Giorgi.
Elevated CD38 antigen expression on CD8+ T cells is a stronger marker for the risk of chronic HIV disease progression to AIDS and death in the Multicenter AIDS Cohort Study than CD4+ cell count, soluble immune activation markers, or combinations of HLA-DR and CD38 expression.
J Acquir Immune Defic Syndr Hum Retrovirol, 16 (1997), pp. 83-92
[4.]
P. Aukrust, N.B. Liabakk, F. Muller, E. Lien, T. Espevik, S.S. Froland.
Serum level of tumor necrosis factor-alpha (TNF alpha) and soluble TNF receptors in human immunodeficiency virus type 1 infection-correlations to clinical, immunologic, and virologic parameters.
J Infect Dis, 169 (1994), pp. 420-424
[5.]
D. Hamann, P.A. Baars, M.H. Rep, B. Hooibrink, S.R. Kerkhof-Garde, M.R. Klein, et al.
Phenotypic and functional separation of memory and effector human CD8+ T cells.
J Exp Med, 186 (1997), pp. 1407-1418
[6.]
D. Israel-Biet, J. Cadranel, K. Beldjord, J.M. Andrieu, A. Jeffrey, P. Even.
Tumor necrosis factor production in HIV-seropositive subjects. Relationships with lung opportunistic infections and HIV expression in alveolar macrophages.
J Immunol, 147 (1991), pp. 490-497
[7.]
A.S. Lau, B.R. Williams.
The role of interferon and tumor necrosis factor in the pathogenesis of AIDS.
J Exp Pathol, 5 (1990), pp. 111-122
[8.]
J.F. Salazar-González, O. Martínez-Maza, N. Aziz, J.A. Kolberg, T. Yeghiazarian, L.P. Shen, et al.
Relationship of plasma HIVRNA levels and levels of TNF-alpha and immune activation products in HIVinfection.
Clin Immunol Immunopathol, 84 (1997), pp. 36-45
[9.]
S. Than, R. Hu, N. Oyaizu, J. Romano, X. Wang, S. Sheikh, et al.
Cytokine pattern in relation to disease progression in human immunodeficiency virus-infected children.
J Infect Dis, 175 (1997), pp. 47-56
[10.]
E. Obregón, C. Börner, J. Navarro, M.D. Gurbindo, E. Fernández-Cruz, M.A. Muñoz-Fernández.
Elevated leels of circulating intercellular adhesion molecule 1 and tumor necrosis factor a in the serum of children vertically infection with HIV-1. Pediatric AIDS and HIV Infection.
Fetus and adolescent, 7 (1996), pp. 413-417
[11.]
C.C. Brown, G. Poli, N. Lubaki, M. St. Louis, F. Davachi, L. Musey, et al.
Elevated levels of tumor necrosis factor-alpha in Zairian neonate plasmas: implications for perinatal infection with the human immunodeficiency virus.
J Infect Dis, 169 (1994), pp. 975-980
[12.]
E.J. Duh, W.J. Maury, T.M. Folks, A.S. Fauci, A.B. Rabson.
Tumor necrosis factor alpha activates human immunodeficiency virus type 1 throughinduction of nuclear factor binding to the NF-kappa B sites in the long terminal repeat.
Am J Obstet Gynecol, 161 (1989), pp. 501-502
[13.]
M.A. Muñoz-Fernández, J. Navarro, A. García, C. Punzón, E. Fernández-Cruz, M. Fresno.
Replication of human immunodeficiency virus-1 in primary human T cells is dependent on the autocrine secretion of tumor necrosis factor through the control of nuclear factor-kappa B activation.
J Allergy Clin Immunol, 100 (1997), pp. 838-845
[14.]
A. Vyakarman, J. McKeating, A. Meager, P.C. Beverley.
Tumour necrosis factors (alpha, beta) induced by HIV-1 in peripheral blood mononuclear cells potentiate virus replication.
Aids, 4 (1990), pp. 21-27
[15.]
M.P. Bevilacqua.
Endothelial-leukocyte adhesion molecules.
Annu Rev Immunol, 11 (1993), pp. 767-804
[16.]
C.A. Dinarello.
Biologic basis for interleukin-1 in disease.
Blood, 87 (1996), pp. 2096-2147
[17.]
F. Puppo, S. Brenci, M. Scudeletti, L. Lanza, O. Bosco, F. Indiveri.
Elevated serum levels of circulating intercellular adhesion molecule-1 in HIV infection.
Aids, 7 (1993), pp. 593-594
[18.]
J. Most, R. Zangerle, M. Herold, D. Fuchs, H. Wachter, P. Fritsch, et al.
Elevated concentrations of circulating intercellular adhesion molecule 1 (ICAM-1) inHIV-1 infection.
J Acquir Immune Defic Syndr, 6 (1993), pp. 221-226
[19.]
M. Tsujisaki, K. Imai, H. Hirata, Y. Hanzawa, J. Masuya, T. Nakano, et al.
Detection of circulating intercellular adhesion molecule-1 antigen in malignant diseases.
Clin Exp Immunol, 85 (1991), pp. 3-8
[20.]
M.A. Muñoz-Fernández, E. Obregón, J. Navarro, C. Borner, M.D. Gurbindo, T.H. Sampelayo.
Relationship of virologic, immunologic and clinical parameters in infants with vertically acquired humanimmunodeficiency virus type 1 infection.
Pediatr Res, 40 (1996), pp. 597-602
[21.]
CDCP..
Center for Diseases Control Prevention. Revised classification systemfor HIV-1 infection in children less than 13 years of age.
Mmwr, 43 (1994), pp. 1-13
[22.]
S. Resino, J.L. Jiménez, D. Gurbindo, M.A. Muñoz-Fernández.
Marcadores predictivos de supervivencia en niños menores de 12 meses de edad infectados verticalmente por el virus de la inmunodeficiencia humana.
Med Clin (Barc), 113 (1999), pp. 561-566
[23.]
G. Poli, A. Kinter, J.S. Justement, J.H. Kehrl, P. Bressler, S. Stanley, et al.
Tumor necrosis factor alpha functions in an autocrine manner in the induction of human immunodeficiency virus expression.
Proc Natl Acad Sci USA, 87 (1990), pp. 782-795
[24.]
G. Herbein, S. Keshav, M. Collin, L.J. Montaner, S. Gordon.
HIV-1 induces tumour necrosis factor and IL-1 gene expression in-primary human macrophages independent of productive infection.
Clin Exp Immunol, 95 (1994), pp. 442-449
[25.]
K. Hestdal, P. Aukrust, F. Muller, E. Lien, V. Bjerkeli, T. Espevik, et al.
Dysregulation of membrane-bound tumor necrosis factor-alpha and tumor necrosis factor receptors on mononuclear cells in human immunodeficiency virus type 1 infection: low percentage of p75-tumor necrosis factor receptor positive cells in patients with advanced disease and high viral load.
Pediatr Infec Dis J, 16 (1997), pp. 963-967
[26.]
L. Monno, G.B. Zimatore, M. Di Stefano, A. Appice, P. Livrea, G. Angarano.
Reduced concentrations of HIV-RNA and TNF-alpha coexist in CSF of AIDS patients with progressive multifocal leukoencephalopathy.
J Neurol Neurosurg Psychiatry, 67 (1999), pp. 369-373
[27.]
L.M. Mofenson, J. Korelitz, W.A. Meyer 3rd, J. Bethel, K. Rich, S. Pahwa, et al.
The relationship between serum human immunodeficiency virus type 1 (HIV-1) RNA level, CD4 lymphocyte percent, and long-term mortality risk in HIV-1-infected children. National Institute of Child Health and Human Development IntravenousImmunoglobulinClinical Trial Study Group.
J Infect Dis, 175 (1997), pp. 1029-1038
[28.]
S. Resino, M.D. Gurbindo, J.M. Bellón, S. Sánchez-Ramón, M.A. Muñoz-Fernández.
Predictive markers of clinical outcome in vertically HIV-1 infected infants, a prospective longitudinal study.
Pediatr Res, 47 (2000), pp. 1-7
[29.]
G. Poli, A. Fauci.
Role of cytokines in the pathogenesis of human immunodeficiency virus infection.
Human cytokines: their role in disease and therapy, pp. 421-449
[30.]
T. Matsuyama, N. Kobayashi, N. Yamamoto.
Cytokines and HIV infection: is Aids a tumor necrosis factor disease?.
Aids, 5 (1991), pp. 1405-1417
[31.]
Resino S, Muñoz-Fernández MA. Marcadores predictivos de evolución de la infección pediátrica por el virus de la inmunodeficiencia humana tipo 1. Acta Pediatr Esp 2000 (en prensa).
[32.]
M. Feldmann, M.J. Elliott, J.N. Woody, R.N. Maini.
Anti-tumor necrosis factor-alpha therapy of rheumatoid arthritis.
Adv Immunol, 64 (1997), pp. 283-350
[33.]
D.M. Meyer, M.L. Dustin, C.P. Carron.
Characterization of intercellular adhesion molecule-1 ectodomain (sICAM-1) as an inhibitor of lymphocyte function-associated molecule-1 interaction with ICAM-1.
J Immunol, 155 (1995), pp. 3578-3584
Copyright © 2000. Asociación Española de Pediatría
Descargar PDF
Idiomas
Anales de Pediatría
Opciones de artículo
Herramientas
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?