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        "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Estudiar el valor predictivo de marcadores inmunol&#243;gicos&#44; virol&#243;gicos y par&#225;metros cl&#237;nicos en la din&#225;mica de progresi&#243;n a muerte durante el seguimiento de una cohorte de 43 ni&#241;os infectados por el VIH-1&#46;</p> <span class="elsevierStyleSectionTitle">Pacientes y m&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo en 43 ni&#241;os infectados verticalmente por el VIH-1&#44; menores de 12 meses de edad &#40;rango&#44; 0-11&#44;80 meses&#41; que no hab&#237;an recibido tratamiento antiretroviral en el momento de su inclusi&#243;n en el estudio&#46; La cin&#233;tica de replicaci&#243;n y el fenotipo de los aislados virales se determin&#243; por cocultivo en CMSP y en MT-2&#44; respectivamente&#46; La carga viral se cuantific&#243; en plasma utilizando el m&#233;todo estandarizado de RT-PCR de Roche&#46; Las subpoblaciones linfocitarias se determinaron por citometr&#237;a de flujo</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Realizamos un an&#225;lisis multivariante de Cox&#44; obteniendo un riesgo relativo de 6&#44;42 &#40;intervalo de confianza del 95&#37;&#44; 1&#44;28-32&#44;03&#41;&#59; &#40;p &#61; 0&#44;023&#41; para los ni&#241;os con una mediana de carga viral superior a 5 log10 copias&#47;ml y de 6&#44;84&#40;intervalo de confianza del 95&#37;&#44; 1&#44;52-30&#44;69&#41;&#59; &#40;p &#61; 0&#44;012&#41; para ni&#241;os con cin&#233;tica de replicaci&#243;n R&#47;A&#46; Tambi&#233;n estudiamos el valor predictivo de los s&#237;ntomas cl&#237;nicos y observamos que los s&#237;ntomas con mayor valor predictivo de progresi&#243;n a muerte fueron la encefalopat&#237;a progresiva &#40;3&#44;60 &#91;IC 95&#37;&#59; 0&#44;92-14&#44;06&#59; p &#61; 0&#44;065&#93;&#41; y la cardiopat&#237;a &#40;6&#44;29 &#91;IC 95&#37;&#58; 1&#44;59 - 24&#44;85&#59; p &#61; 0&#44;008&#93;&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Los marcadores inmunol&#243;gicos y virol&#243;gicos predictivos de progresi&#243;n a muerte m&#225;s importantes fueron la mediana de carga viral superior a 5 log10 y los aislados virales con cin&#233;tica de replicaci&#243;n R&#47;A a lo largo del estudio&#46; Adem&#225;s&#44; la encefalopat&#237;a progresiva y la cardiopat&#237;a se comportaron como marcadores independientes predictivos de progresi&#243;n a muerte&#46;</p>"
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        "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">To study the relationship among clinical symptoms and biological markers as predictive value of progression to death in HIV-1 vertically infected infants</p> <span class="elsevierStyleSectionTitle">Patient and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">We carry out a prospective study in 43 HIV-1 infants with a mean age of 4&#46;27 &#40;range&#58; 0-11&#46;8 months&#41;&#46; None of the infant&#39;s mothers had received any antiviral treatment during pregnancy&#46; None of the infants were breastfed&#46; They were routinely assessed for clinical symptoms during follow-up</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Cox regression analysis was used to study the hazard ratio &#40;HR&#41; of progression to death&#46; For the median viral load &#62; 5 log10&#44; the HR was 6&#46;42 &#40;95&#37; CI&#44; 1&#46;28-32&#46;03&#41; &#40;p &#61; 0&#46;023&#41; and 6&#46;84 &#40;95&#37; CI&#44; 1&#46;52-30&#44;69&#41; &#40;p &#61; 0&#46;012&#41; for biological phenotype of viral isolates with rapid replication and high titter &#40;R&#47;H-X4&#41;&#46; We also study the predictive value of the clinical symptoms and we observe that the symptoms with more HR of progression to death were the progressive encephalopathy &#40;3&#46;60 &#91;95&#37; CI&#44; 0&#46;92-14&#46;06&#59; p &#61; 0&#46;065&#93;&#41; and the cardiopathy &#40;6&#46;29 &#91;95&#37; CI&#44; 1&#46;59-24&#46;85&#59; p &#61; 0&#46;008&#93;&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Our data indicate that viral load &#62; 5 log10 and biological phenotype R&#47;H-X4 of virus isolates along the study are predictive markers of progression to death&#46; In addition&#44; the progressive encephalopathy and cardiopathy were also markers of progression death&#46;</p>"
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                          "autores" => array:6 [
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                        "link" => array:1 [
                          0 => array:2 [
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                            2 => "D&#46; Martin"
                            3 => "J&#46; Esinhart"
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                            3 => "M&#46;S&#46; Hirsch"
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                        "link" => array:1 [
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "P&#46;E&#46; Palumbo"
                            1 => "S&#46; Kwok"
                            2 => "S&#46; Waters"
                            3 => "Y&#46; Wesley"
                            4 => "D&#46; Lewis"
                            5 => "N&#46; Mekinney"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pediatr"
                        "fecha" => "1995"
                        "volumen" => "126"
                        "paginaInicial" => "592"
                        "paginaFinal" => "595"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7699539"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Age-and time-related changes in extracellular viral load in children vertically infected by human immunodeficiency virus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "K&#46; Mcintosh"
                            1 => "A&#46; Shevitz"
                            2 => "D&#46; Zaknun"
                            3 => "J&#46; Kornegoy"
                            4 => "P&#46; Ctiotis"
                            5 => "N&#46; Korttias"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Infect Dis J"
                        "fecha" => "1996"
                        "volumen" => "15"
                        "paginaInicial" => "1087"
                        "paginaFinal" => "1091"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8970217"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The relationship between serum HIV-1 RNA levels&#44; CD4 lymphocyte percent&#44; and long-term mortality risk in HIV-1 infected children"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "L&#46;M&#46; Mofenson"
                            1 => "J&#46; Korelitz"
                            2 => "W&#46;A&#46; Meyer"
                            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"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Viral load and disease progression in infants infected with human immunodeficiency virus tipe 1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "W&#46;T&#46; Shearer"
                            1 => "T&#46;C&#46; Quinn"
                            2 => "P&#46; La Russa"
                            3 => "J&#46;F&#46; Lew"
                            4 => "L&#46; Mofenson"
                            5 => "S&#46; Almy"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJM199705083361901"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "1997"
                        "volumen" => "336"
                        "paginaInicial" => "1337"
                        "paginaFinal" => "1342"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9134873"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "HIV Collaborative Retrovirology Perinatal Group USA&#46; HIV detection&#44; virus load&#44; and disease progression in perinatally infected infants"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "M&#46;K&#46; Cowles"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:5 [
                        "paginaInicial" => "25"
                        "paginaFinal" => "28"
                        "serieVolumen" => "2"
                        "serieTitulo" => "12th World Aids Conference Book&#46; Geneve &#40;Switzerland&#41;&#44; June 28-July 3&#44; 1998"
                        "serieFecha" => "1998"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Predictive value of quantitative plasma HIV RNA and CD4&#43; lymphocyte count in HIV-1 infected infants and children"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "P&#46;E&#46; Palumbo"
                            1 => "C&#46; Raskino"
                            2 => "S&#46; Fiscus"
                            3 => "S&#46; Pahwa"
                            4 => "M&#46;G&#46; Fowler"
                            5 => "S&#46;A&#46; Spector"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Jama"
                        "fecha" => "1998"
                        "volumen" => "279"
                        "paginaInicial" => "756"
                        "paginaFinal" => "761"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9508151"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Early prognostic indicators in primary perinatal human immunodeficiency virus type 1 infection&#58; importance ofviral RNA and the timing of transmission on long-term outcome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "R&#46;E&#46; Dickover"
                            1 => "M&#46; Dillon"
                            2 => "K&#46;M&#46; Leung"
                            3 => "P&#46; Krogstad"
                            4 => "S&#46; Plaeger"
                            5 => "S&#46; Kwok"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Infect Dis"
                        "fecha" => "1998"
                        "volumen" => "178"
                        "paginaInicial" => "375"
                        "paginaFinal" => "387"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9697717"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evaluation of surrogate markers and clinical outcomesin two-years follow-up of eighty-six human immunodeficiency virus-infected pediatric patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46;E&#46; Valentine"
                            1 => "C&#46;R&#46; Jackson"
                            2 => "C&#46; Vavro"
                            3 => "Wilfertom"
                            4 => "D&#46; Mc Clernon"
                            5 => "M&#46; St&#46; Clair"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Infect Dis J"
                        "fecha" => "1998"
                        "volumen" => "17"
                        "paginaInicial" => "18"
                        "paginaFinal" => "23"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9469389"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hihg viral load in children long-term non progressor vertically infected with HIV-1&#46; Immunologyc characterization"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46;A&#46; Mu&#241;oz-Fern&#225;ndez"
                            1 => "S&#46; Resino"
                            2 => "J&#46; Navarro"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:5 [
                        "paginaInicial" => "45"
                        "paginaFinal" => "49"
                        "serieVolumen" => "2"
                        "serieTitulo" => "12th World Aids Conference Book&#46; Geneve &#40;Switzerland&#41;&#44; June 28-July3&#44; 1998"
                        "serieFecha" => "1998"
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                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Replicative properties of human immunodeficiencyvirus from patients with varying severity of HIV infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "B&#46;J&#46; Asjo"
                            1 => "L&#46; Morfeldt-Manson"
                            2 => "J&#46; Albert"
                            3 => "G&#46; Biberfeld"
                            4 => "A&#46; Karlsson"
                            5 => "K&#46; Lidman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "1986"
                        "volumen" => "2"
                        "paginaInicial" => "660"
                        "paginaFinal" => "662"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2570907"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Association between biological properties of human immunodeficiency virus variant and risk for Aids mortality"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46; Tersmette"
                            1 => "J&#46;M&#46; Lange"
                            2 => "R&#46;E&#46; De Goede"
                            3 => "F&#46; De Wolf"
                            4 => "J&#46;K&#46; Feftink-Shattenkerk"
                            5 => "P&#46;T&#46; Schellekens"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "1989"
                        "volumen" => "6"
                        "paginaInicial" => "983"
                        "paginaFinal" => "985"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Differential syncytium-inducing capacity of human immunodeficiency virus isolates&#58; frequent detection of syncytium-inducing isolates in patients with acquired immunodeficienci syndrome &#40;Aids&#41; and Aids-related complex&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "MJMA&#46; Tersmette"
                            1 => "REY&#46; De Goede"
                            2 => "BMJ&#46; Al"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Virol"
                        "fecha" => "1988"
                        "volumen" => "62"
                        "paginaInicial" => "2026"
                        "paginaFinal" => "2032"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3130494"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            17 => array:3 [
              "identificador" => "bib0090"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evidence for a role of virulent human immunodeficiency virus &#40;HIV&#41; variants in the pathogenesis of Aids obtained from studies on a panel of sequential HIV isolates"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
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                            1 => "R&#46;A&#46; Gruters"
                            2 => "F&#46; De Wolf"
                            3 => "R&#46;E&#46; De Goede"
                            4 => "J&#46;M&#46; Lange"
                            5 => "P&#46;T&#46; Schellekens"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Virol"
                        "fecha" => "1989"
                        "volumen" => "63"
                        "paginaInicial" => "2118"
                        "paginaFinal" => "2125"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2564898"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biologicalal phenotype of human immunodeficiency virus tipe 1 clones at different stagesof infection&#58; progression of the disease is associated with a shift from monocytotropic to T-cell-tropic virus population"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "H&#46; Schuitemaker"
                            1 => "M&#46; Koot"
                            2 => "N&#46;A&#46; Kootstra"
                            3 => "M&#46;W&#46; Derksen"
                            4 => "R&#46;E&#46; De Goede"
                            5 => "R&#46;P&#46; Van Steenwijk"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Virol"
                        "fecha" => "1992"
                        "volumen" => "66"
                        "paginaInicial" => "1354"
                        "paginaFinal" => "1360"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1738194"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biologicalalproperties of HIV isolates in primary HIV infection&#58; consequences for the subsequent course of infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "C&#46; Nielsen"
                            1 => "C&#46; Pedersen"
                            2 => "J&#46;D&#46; Lundgren"
                            3 => "J&#46; Gerstoft"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Aids"
                        "fecha" => "1993"
                        "volumen" => "7"
                        "paginaInicial" => "1035"
                        "paginaFinal" => "1040"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8104421"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lymphocyte subsets in healthy children during the first 5 years of life"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Y&#46; Denny"
                            1 => "R&#46; Yogev"
                            2 => "R&#46; Gelman"
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Jama"
                        "fecha" => "1992"
                        "volumen" => "267"
                        "paginaInicial" => "1484"
                        "paginaFinal" => "1488"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1347086"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Immunopathogenic mechanism in human immunodeficiency virus &#40;HIV&#41; infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46;S&#46; Fauci"
                            1 => "S&#46;M&#46; Schnittman"
                            2 => "G&#46; Poli"
                            3 => "S&#46; Koenig"
                            4 => "G&#46; Pantaleo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Intern Med"
                        "fecha" => "1991"
                        "volumen" => "114"
                        "paginaInicial" => "678"
                        "paginaFinal" => "693"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1672248"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Markers for progression in HIV infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "JMA&#46; Lange"
                            1 => "F&#46; De Wolf"
                            2 => "J&#46; Goudsmit"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Aids"
                        "fecha" => "1989"
                        "volumen" => "3"
                        "paginaInicial" => "153"
                        "paginaFinal" => "160"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "CD8 lymphocyte counts and serum immunoglobulin a levels early in HIV infection aspredictors of CD4 lymphocyte depletion during 8 years follow- up"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46;N&#46; Philips"
                            1 => "C&#46;A&#46; Sabin"
                            2 => "J&#46; Elford"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Aids"
                        "fecha" => "1993"
                        "volumen" => "7"
                        "paginaInicial" => "975"
                        "paginaFinal" => "980"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8102854"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25&#46;"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "CD8&#43; T-lymphocytes and progresion to Aids in HIV infected men&#58; some observations"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "R&#46;E&#46; Anderson"
                            1 => "S&#46;C&#46; Shiboski"
                            2 => "R&#46; Royce"
                            3 => "N&#46;P&#46; Jewell"
                            4 => "W&#46; Lang"
                            5 => "W&#46; Winkelstein"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Aids"
                        "fecha" => "1991"
                        "volumen" => "5"
                        "paginaInicial" => "213"
                        "paginaFinal" => "215"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1903262"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26&#46;"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prognostic value of an elevated CD8 lymphocyte count in HIV infection&#46; Results of a prospective study of 152 asymptomatic HIV-positive individuals"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S&#46; Chevret"
                            1 => "H&#46; Roquin"
                            2 => "P&#46; Ganne"
                            3 => "J&#46;J&#46; Lefr&#232;re"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Aids"
                        "fecha" => "1992"
                        "volumen" => "6"
                        "paginaInicial" => "1349"
                        "paginaFinal" => "1352"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1361748"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The significance of activationmarkers on CD8 lymphocytes in human immunodeficiency syndrome&#58; staging and prognostic value"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46; Levacher"
                            1 => "F&#46; Hulstaer"
                            2 => "S&#46; Tallet"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Immunol"
                        "fecha" => "1992"
                        "volumen" => "90"
                        "paginaInicial" => "376"
                        "paginaFinal" => "382"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1458674"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Penumocistis carinii pneumonia among US children with perinatally acquired HIV infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "R&#46;J&#46; Simonds"
                            1 => "M&#46;J&#46; Oxtoby"
                            2 => "M&#46;B&#46; Caldwell"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Jama"
                        "fecha" => "1993"
                        "volumen" => "270"
                        "paginaInicial" => "470"
                        "paginaFinal" => "473"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8320786"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neonatal characteristics in rapidly progressive perinatally acquired HIV-1 disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46;J&#46; Mayaux"
                            1 => "M&#46; Burgard"
                            2 => "J&#46;P&#46; Teglas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Jama"
                        "fecha" => "1996"
                        "volumen" => "275"
                        "paginaInicial" => "606"
                        "paginaFinal" => "610"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8594241"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long term Non-progressorsamong children with perinatal HIV- infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "P&#46;A&#46; Tovo"
                            1 => "M&#46; De Martino"
                            2 => "C&#46; Gabino"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Acquir Immune Defic Syndr"
                        "fecha" => "1997"
                        "volumen" => "15"
                        "paginaInicial" => "19"
                        "paginaFinal" => "22"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Disease patterns and survival after acquired immunodeficiency syndrome diagnosis in human immunodeficiency virus infected children"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "C&#46; Morrids"
                            1 => "S&#46;A&#46; Araba-OwoyeleSpector"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Pediatr Infects Dis J"
                        "fecha" => "1996"
                        "volumen" => "15"
                        "paginaInicial" => "321"
                        "paginaFinal" => "328"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Relationship of Virological&#44;Immunological&#44; and Clinical Parameters in Infants with vertically acquired human immunodeficiency virus tipe 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"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Regression models and life tables"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "D&#46;R&#46; Cox"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J R Stat Soc"
                        "fecha" => "1972"
                        "volumen" => "34"
                        "paginaInicial" => "187"
                        "paginaFinal" => "220"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "34&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Zidovudine&#44; didanosine&#44; or both as the initial treatment for symptomatic HIV-infected children"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "J&#46;A&#46; Englund"
                            1 => "C&#46;J&#46; Baker"
                            2 => "C&#46; Raskino"
                            3 => "R&#46;E&#46; McKinney"
                            4 => "B&#46; Petrie"
                            5 => "M&#46;G&#46; Fowler"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJM199706123362403"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "1997"
                        "volumen" => "336"
                        "paginaInicial" => "1704"
                        "paginaFinal" => "1712"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9182213"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            34 => array:3 [
              "identificador" => "bib0175"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect ofintravenous immunoglobulin &#40;IVIG&#41; on CD4&#43; lymphocyte decline in HIV-infected children in a clinical trial of IVIG infection prophylaxis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "L&#46;M&#46; Mofenson"
                            1 => "J&#46; Bethel"
                            2 => "J&#46; Moye Jr"
                            3 => "P&#46; Flyer"
                            4 => "R&#46; Nugent"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "J Acquir Immune Defic Syndr"
                        "fecha" => "1993"
                        "paginaInicial" => "1103"
                        "paginaFinal" => "1113"
                      ]
                    ]
                  ]
                ]
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            35 => array:3 [
              "identificador" => "bib0180"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "CD8 lymphocyte counts and serum immunoglobulin A levels early in HIV infection aspredictors of CD4 lymphocyte depletion during 8 years follow- up"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46;N&#46; Phillips"
                            1 => "C&#46;A&#46; Sabin"
                            2 => "J&#46; Elford"
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Aids"
                        "fecha" => "1993"
                        "volumen" => "7"
                        "paginaInicial" => "975"
                        "paginaFinal" => "980"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8102854"
                            "web" => "Medline"
                          ]
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                    ]
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                ]
              ]
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            36 => array:3 [
              "identificador" => "bib0185"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A controlled Trial of IVIG for prevention serious bacterial infections"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "S&#46;A&#46; Spector"
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                    0 => array:2 [
                      "doi" => "10.1056/NEJM199411033311802"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "1994"
                        "volumen" => "331"
                        "paginaInicial" => "1181"
                        "paginaFinal" => "1187"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7935655"
                            "web" => "Medline"
                          ]
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                      ]
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                ]
              ]
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            37 => array:3 [
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "HIV replication during the first weeks of life"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46; Krivine"
                            1 => "G&#46; Firtion"
                            2 => "L&#46; Cao"
                            3 => "C&#46; Francoual"
                            4 => "R&#46; Henrion"
                            5 => "P&#46; Lebon"
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                        ]
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "1992"
                        "volumen" => "339"
                        "paginaInicial" => "1187"
                        "paginaFinal" => "1189"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1349936"
                            "web" => "Medline"
                          ]
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                      ]
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                  ]
                ]
              ]
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            38 => array:3 [
              "identificador" => "bib0195"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Natural history of human immunodeficiency virus type 1 infection in children&#58; prognostic value of laboratory test on bimodal progression of the disease"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46;M&#46; Duliege"
                            1 => "A&#46; Messiah"
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                            3 => "M&#46; Tardieu"
                            4 => "C&#46; Griscelli"
                            5 => "A&#46; Spira"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Infect Dis J"
                        "fecha" => "1992"
                        "volumen" => "11"
                        "paginaInicial" => "630"
                        "paginaFinal" => "645"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1523073"
                            "web" => "Medline"
                          ]
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                ]
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            39 => array:3 [
              "identificador" => "bib0200"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The Pediatric Aids Siena Workshop II&#46; Markers and determinants of disease progression in children with HIV infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
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                            1 => "C&#46;M&#46; Wilfert"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Aids"
                        "fecha" => "1995"
                        "volumen" => "8"
                        "paginaInicial" => "30"
                        "paginaFinal" => "44"
                      ]
                    ]
                  ]
                ]
              ]
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            40 => array:3 [
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neonatal characteristics in rapidly progressive perinatally acquired HIV-1 disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46;J&#46; Mayaux"
                            1 => "M&#46; Burgard"
                            2 => "J&#46;P&#46; Teglas"
                            3 => "J&#46; Cottalorda"
                            4 => "A&#46; Krivine"
                            5 => "F&#46; Simon"
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                        ]
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Jama"
                        "fecha" => "1996"
                        "volumen" => "275"
                        "paginaInicial" => "606"
                        "paginaFinal" => "610"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8594241"
                            "web" => "Medline"
                          ]
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                ]
              ]
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            41 => array:3 [
              "identificador" => "bib0210"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Paediatric HIV infection"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "G&#46; Scarlatti"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(95)11030-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "1996"
                        "volumen" => "348"
                        "paginaInicial" => "863"
                        "paginaFinal" => "868"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8826814"
                            "web" => "Medline"
                          ]
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                      ]
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                ]
              ]
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            42 => array:3 [
              "identificador" => "bib0215"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical significance of human immunodeficiency virus type 1 phenotypes in infected children"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "L&#46;T&#46; Spencer"
                            1 => "M&#46;T&#46; Ogino"
                            2 => "W&#46;M&#46; Danker"
                            3 => "S&#46;A&#46; Spector"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Infect Dis"
                        "fecha" => "1994"
                        "volumen" => "169"
                        "paginaInicial" => "491"
                        "paginaFinal" => "495"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7908924"
                            "web" => "Medline"
                          ]
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                    ]
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                ]
              ]
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            43 => array:3 [
              "identificador" => "bib0220"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prognostic value of HIV-1 biologicalal phenotype for rate of CD4&#43; count cell depletion and progression to Aids"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46; Koot"
                            1 => "I&#46;P&#46; Keet"
                            2 => "A&#46;H&#46; Vos"
                            3 => "De Goedere"
                            4 => "M&#46;T&#46; Roos"
                            5 => "R&#46;A&#46; Coutinho"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Intern Med"
                        "fecha" => "1993"
                        "volumen" => "118"
                        "paginaInicial" => "681"
                        "paginaFinal" => "688"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8096374"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "45&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Immunological and virological markers of disease progression in HIV-1 infected children"
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                          "etal" => false
                          "autores" => array:5 [
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                            2 => "R&#46;A&#46; Obreg&#243;n&#44; Arias"
                            3 => "M&#46;D&#46; Gurbindo"
                            4 => "T&#46;H&#46; Sampelayo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Acta Paediatr"
                        "fecha" => "1997"
                        "volumen" => "421"
                        "paginaInicial" => "46"
                        "paginaFinal" => "51"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "46&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Plasma viremia and virus phenotype are correlates of disease progression in vertically human immunodeficiency virus type 1-infected children"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
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                            1 => "M&#46;C&#46; Colombo"
                            2 => "G&#46; Colucci"
                            3 => "A&#46; Vigano"
                            4 => "C&#46; Riva"
                            5 => "L&#46; Papagno"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Infect Dis J"
                        "fecha" => "1997"
                        "volumen" => "16"
                        "paginaInicial" => "205"
                        "paginaFinal" => "211"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9041602"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "47&#46;"
              "referencia" => array:1 [
                0 => array:2 [
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                          "etal" => false
                          "autores" => array:3 [
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                            1 => "F&#46; Veber"
                            2 => "C&#46; Griscelli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:3 [
                        "fecha" => "1988"
                        "editorial" => "Berrebi"
                        "editorialLocalizacion" => "Toulouse"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "48&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "Italian Multicentry study&#46; Epidemiology&#44; clinical features and prognostic factors of pediatric HIV infection"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "1988"
                        "volumen" => "2"
                        "paginaInicial" => "1043"
                        "paginaFinal" => "1046"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2572777"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "49&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Morbidity and mortality in European Children vertically infected by HIV-1&#58; The French prospective study and the European collaborative study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S&#46; Blanches"
                            1 => "M&#46; Newell"
                            2 => "M&#46; Mayaux"
                            3 => "A&#46;T&#46; Dunn"
                            4 => "J&#46;P&#46; Teglas"
                            5 => "C&#46; Rouzioux"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Acquir Immune Def Syndrome"
                        "fecha" => "1997"
                        "volumen" => "14"
                        "paginaInicial" => "1442"
                        "paginaFinal" => "1450"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "50&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Advances and problems in the diagnosis of human immunodeficiency virus infection in infants"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46;F&#46; Rogers"
                            1 => "C&#46;Y&#46; Ou"
                            2 => "B&#46; Kilbourne"
                            3 => "G&#46; Schochetman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Pediatr Infect Dis"
                        "fecha" => "1991"
                        "volumen" => "10"
                        "paginaInicial" => "523"
                        "paginaFinal" => "531"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "51&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Survival in children perinatally acquired human immunodeficiency virus type 1 infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "G&#46;B&#46; Scott"
                            1 => "C&#46; Hutto"
                            2 => "R&#46;W&#46; Makuch"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJM198912283212604"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "1989"
                        "volumen" => "321"
                        "paginaInicial" => "1791"
                        "paginaFinal" => "1796"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2594038"
                            "web" => "Medline"
                          ]
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                    ]
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                ]
              ]
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Vol. 52. Núm. 2.
Páginas 138-147 (febrero 2000)
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Vol. 52. Núm. 2.
Páginas 138-147 (febrero 2000)
Acceso a texto completo
Manifestaciones clínicas y marcadores biológicos en la historia natural de la infección por el VIH-1 en niños infectados verticalmente. Estudio longitudinal
Clinical manifestations and biological markers in the natural history of hiv-1 infection. Longitudinal study
Visitas
6005
S. Resinoa, J.M. Bellóna, J.L. Jiméneza, D. Gurbindob, M.A. Muñoz-Fernándeza,
Autor para correspondencia
Mmunoz@cbm.uam.es

Correspondencia: Dra. M.A. Muñoz-Fernández. Servicio de Inmunología. Hospital General Universitario Gregorio Marañón. Dr. Esquerdo, 46. 28007 Madrid.
a Servicio de Inmunología. Hospital Central Universitario Gregorio Marañón. Madrid.
b Sección de Inmuno-Pediatría. Hospital Central Universitario Gregorio Marañón. Madrid.
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Estadísticas
Objetivo

Estudiar el valor predictivo de marcadores inmunológicos, virológicos y parámetros clínicos en la dinámica de progresión a muerte durante el seguimiento de una cohorte de 43 niños infectados por el VIH-1.

Pacientes y métodos

Estudio prospectivo en 43 niños infectados verticalmente por el VIH-1, menores de 12 meses de edad (rango, 0-11,80 meses) que no habían recibido tratamiento antiretroviral en el momento de su inclusión en el estudio. La cinética de replicación y el fenotipo de los aislados virales se determinó por cocultivo en CMSP y en MT-2, respectivamente. La carga viral se cuantificó en plasma utilizando el método estandarizado de RT-PCR de Roche. Las subpoblaciones linfocitarias se determinaron por citometría de flujo

Resultados

Realizamos un análisis multivariante de Cox, obteniendo un riesgo relativo de 6,42 (intervalo de confianza del 95%, 1,28-32,03); (p = 0,023) para los niños con una mediana de carga viral superior a 5 log10 copias/ml y de 6,84(intervalo de confianza del 95%, 1,52-30,69); (p = 0,012) para niños con cinética de replicación R/A. También estudiamos el valor predictivo de los síntomas clínicos y observamos que los síntomas con mayor valor predictivo de progresión a muerte fueron la encefalopatía progresiva (3,60 [IC 95%; 0,92-14,06; p = 0,065]) y la cardiopatía (6,29 [IC 95%: 1,59 - 24,85; p = 0,008]).

Conclusiones

Los marcadores inmunológicos y virológicos predictivos de progresión a muerte más importantes fueron la mediana de carga viral superior a 5 log10 y los aislados virales con cinética de replicación R/A a lo largo del estudio. Además, la encefalopatía progresiva y la cardiopatía se comportaron como marcadores independientes predictivos de progresión a muerte.

Palabras clave:
VIH-1
Niños
Carga viral
Fenotipo biológico
Linfocitos T CD4+
Supervivencia
Marcadores pronósticos
Objective

To study the relationship among clinical symptoms and biological markers as predictive value of progression to death in HIV-1 vertically infected infants

Patient and methods

We carry out a prospective study in 43 HIV-1 infants with a mean age of 4.27 (range: 0-11.8 months). None of the infant's mothers had received any antiviral treatment during pregnancy. None of the infants were breastfed. They were routinely assessed for clinical symptoms during follow-up

Results

Cox regression analysis was used to study the hazard ratio (HR) of progression to death. For the median viral load > 5 log10, the HR was 6.42 (95% CI, 1.28-32.03) (p = 0.023) and 6.84 (95% CI, 1.52-30,69) (p = 0.012) for biological phenotype of viral isolates with rapid replication and high titter (R/H-X4). We also study the predictive value of the clinical symptoms and we observe that the symptoms with more HR of progression to death were the progressive encephalopathy (3.60 [95% CI, 0.92-14.06; p = 0.065]) and the cardiopathy (6.29 [95% CI, 1.59-24.85; p = 0.008]).

Conclusions

Our data indicate that viral load > 5 log10 and biological phenotype R/H-X4 of virus isolates along the study are predictive markers of progression to death. In addition, the progressive encephalopathy and cardiopathy were also markers of progression death.

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Bibliografía
[1.]
J.W. Mellors, A. Muñoz, J.V. Giorgi, J.B. Morgolick, C.J. Tassoni, P. Gupta.
Plasma viral load and CD4+ lymphocytes as prognosticmarkers of HIV-1 infection.
Ann Intern Med, 126 (1997), pp. 946-954
[2.]
W.A. O'Brien, P.M. Hartigan, D. Martin, J. Esinhart, A. Hill, Benorts.
Changes in plasma HIV-1 RNA and CD4+ lymphocytes counts and the risk of progression to Aids.
N Engl J Med, 334 (1996), pp. 426-431
[3.]
C.C. Carpenter, M.A. Fischl, S.M. Hammer, M.S. Hirsch, D.M. Jaconbson, D.A. Katzenstein.
Antiretroviral therapy for HIV infection in 1996: recommendations of an international panel.
Jama, 276 (1996), pp. 146-154
[4.]
B.G. Gazzard, G.J. Moyle, J. Weber, M. Johnson, J.S. Bingham, R. Brettle.
British HIV Association guidelines for antiretroviral treatment of HIV seropositive individuals..
Lancet, 349 (1997), pp. 1086-1092
[5.]
A. De Rossi, S. Masiero, C. Giaquinto, E. Rugo, M. Conor, M. Giaca.
Dinamics of viral replication in infants with vertically acquired human immunodeficiency virus tipe 1 infection.
J Clin Invest, 97 (1996), pp. 323-330
[6.]
P.E. Palumbo, S. Kwok, S. Waters, Y. Wesley, D. Lewis, N. Mekinney.
Viral measurement by polymerase chain reactionbased assays in human immunodeficiency virus-infected infants.
J Pediatr, 126 (1995), pp. 592-595
[7.]
K. Mcintosh, A. Shevitz, D. Zaknun, J. Kornegoy, P. Ctiotis, N. Korttias.
Age-and time-related changes in extracellular viral load in children vertically infected by human immunodeficiency virus.
Pediatr Infect Dis J, 15 (1996), pp. 1087-1091
[8.]
L.M. Mofenson, J. Korelitz, W.A. Meyer, J. Bethel, K. Rich, S. Pahwa.
The relationship between serum HIV-1 RNA levels, CD4 lymphocyte percent, and long-term mortality risk in HIV-1 infected children.
J Infect Dis, 175 (1997), pp. 1029-1038
[9.]
W.T. Shearer, T.C. Quinn, P. La Russa, J.F. Lew, L. Mofenson, S. Almy.
Viral load and disease progression in infants infected with human immunodeficiency virus tipe 1.
N Engl J Med, 336 (1997), pp. 1337-1342
[10.]
M.K. Cowles.
HIV Collaborative Retrovirology Perinatal Group USA. HIV detection, virus load, and disease progression in perinatally infected infants.
pp. 25-28
[11.]
P.E. Palumbo, C. Raskino, S. Fiscus, S. Pahwa, M.G. Fowler, S.A. Spector.
Predictive value of quantitative plasma HIV RNA and CD4+ lymphocyte count in HIV-1 infected infants and children.
Jama, 279 (1998), pp. 756-761
[12.]
R.E. Dickover, M. Dillon, K.M. Leung, P. Krogstad, S. Plaeger, S. Kwok.
Early prognostic indicators in primary perinatal human immunodeficiency virus type 1 infection: importance ofviral RNA and the timing of transmission on long-term outcome.
J Infect Dis, 178 (1998), pp. 375-387
[13.]
M.E. Valentine, C.R. Jackson, C. Vavro, Wilfertom, D. Mc Clernon, M. St. Clair.
Evaluation of surrogate markers and clinical outcomesin two-years follow-up of eighty-six human immunodeficiency virus-infected pediatric patients.
Pediatr Infect Dis J, 17 (1998), pp. 18-23
[14.]
M.A. Muñoz-Fernández, S. Resino, J. Navarro.
Hihg viral load in children long-term non progressor vertically infected with HIV-1. Immunologyc characterization.
pp. 45-49
[15.]
B.J. Asjo, L. Morfeldt-Manson, J. Albert, G. Biberfeld, A. Karlsson, K. Lidman.
Replicative properties of human immunodeficiencyvirus from patients with varying severity of HIV infection.
Lancet, 2 (1986), pp. 660-662
[16.]
M. Tersmette, J.M. Lange, R.E. De Goede, F. De Wolf, J.K. Feftink-Shattenkerk, P.T. Schellekens.
Association between biological properties of human immunodeficiency virus variant and risk for Aids mortality.
Lancet, 6 (1989), pp. 983-985
[17.]
MJMA. Tersmette, REY. De Goede, BMJ. Al.
Differential syncytium-inducing capacity of human immunodeficiency virus isolates: frequent detection of syncytium-inducing isolates in patients with acquired immunodeficienci syndrome (Aids) and Aids-related complex..
J Virol, 62 (1988), pp. 2026-2032
[18.]
MJMA. Tersmette, R.A. Gruters, F. De Wolf, R.E. De Goede, J.M. Lange, P.T. Schellekens.
Evidence for a role of virulent human immunodeficiency virus (HIV) variants in the pathogenesis of Aids obtained from studies on a panel of sequential HIV isolates.
J Virol, 63 (1989), pp. 2118-2125
[19.]
H. Schuitemaker, M. Koot, N.A. Kootstra, M.W. Derksen, R.E. De Goede, R.P. Van Steenwijk.
Biologicalal phenotype of human immunodeficiency virus tipe 1 clones at different stagesof infection: progression of the disease is associated with a shift from monocytotropic to T-cell-tropic virus population.
J Virol, 66 (1992), pp. 1354-1360
[20.]
C. Nielsen, C. Pedersen, J.D. Lundgren, J. Gerstoft.
Biologicalalproperties of HIV isolates in primary HIV infection: consequences for the subsequent course of infection.
Aids, 7 (1993), pp. 1035-1040
[21.]
Y. Denny, R. Yogev, R. Gelman.
Lymphocyte subsets in healthy children during the first 5 years of life.
Jama, 267 (1992), pp. 1484-1488
[22.]
A.S. Fauci, S.M. Schnittman, G. Poli, S. Koenig, G. Pantaleo.
Immunopathogenic mechanism in human immunodeficiency virus (HIV) infection.
Ann Intern Med, 114 (1991), pp. 678-693
[23.]
JMA. Lange, F. De Wolf, J. Goudsmit.
Markers for progression in HIV infection.
Aids, 3 (1989), pp. 153-160
[24.]
A.N. Philips, C.A. Sabin, J. Elford.
CD8 lymphocyte counts and serum immunoglobulin a levels early in HIV infection aspredictors of CD4 lymphocyte depletion during 8 years follow- up.
Aids, 7 (1993), pp. 975-980
[25.]
R.E. Anderson, S.C. Shiboski, R. Royce, N.P. Jewell, W. Lang, W. Winkelstein.
CD8+ T-lymphocytes and progresion to Aids in HIV infected men: some observations.
Aids, 5 (1991), pp. 213-215
[26.]
S. Chevret, H. Roquin, P. Ganne, J.J. Lefrère.
Prognostic value of an elevated CD8 lymphocyte count in HIV infection. Results of a prospective study of 152 asymptomatic HIV-positive individuals.
Aids, 6 (1992), pp. 1349-1352
[27.]
M. Levacher, F. Hulstaer, S. Tallet.
The significance of activationmarkers on CD8 lymphocytes in human immunodeficiency syndrome: staging and prognostic value.
Clin Exp Immunol, 90 (1992), pp. 376-382
[28.]
R.J. Simonds, M.J. Oxtoby, M.B. Caldwell.
Penumocistis carinii pneumonia among US children with perinatally acquired HIV infection.
Jama, 270 (1993), pp. 470-473
[29.]
M.J. Mayaux, M. Burgard, J.P. Teglas.
Neonatal characteristics in rapidly progressive perinatally acquired HIV-1 disease.
Jama, 275 (1996), pp. 606-610
[30.]
P.A. Tovo, M. De Martino, C. Gabino.
Long term Non-progressorsamong children with perinatal HIV- infection.
J Acquir Immune Defic Syndr, 15 (1997), pp. 19-22
[31.]
C. Morrids, S.A. Araba-OwoyeleSpector.
Disease patterns and survival after acquired immunodeficiency syndrome diagnosis in human immunodeficiency virus infected children.
Pediatr Infects Dis J, 15 (1996), pp. 321-328
[32.]
M.A. Muñoz-Fernández, E. Obregón, J. Navarro, C. Borner, M.D. Gurbindo, T.H. Sampelayo.
Relationship of Virological,Immunological, and Clinical Parameters in Infants with vertically acquired human immunodeficiency virus tipe 1 infection.
Pediatr Res, 40 (1996), pp. 597-602
[33.]
D.R. Cox.
Regression models and life tables.
J R Stat Soc, 34 (1972), pp. 187-220
[34.]
J.A. Englund, C.J. Baker, C. Raskino, R.E. McKinney, B. Petrie, M.G. Fowler.
Zidovudine, didanosine, or both as the initial treatment for symptomatic HIV-infected children.
N Engl J Med, 336 (1997), pp. 1704-1712
[35.]
L.M. Mofenson, J. Bethel, J. Moye Jr, P. Flyer, R. Nugent.
Effect ofintravenous immunoglobulin (IVIG) on CD4+ lymphocyte decline in HIV-infected children in a clinical trial of IVIG infection prophylaxis.
J Acquir Immune Defic Syndr, (1993), pp. 1103-1113
[36.]
A.N. Phillips, C.A. Sabin, J. Elford.
CD8 lymphocyte counts and serum immunoglobulin A levels early in HIV infection aspredictors of CD4 lymphocyte depletion during 8 years follow- up.
Aids, 7 (1993), pp. 975-980
[37.]
S.A. Spector.
A controlled Trial of IVIG for prevention serious bacterial infections.
N Engl J Med, 331 (1994), pp. 1181-1187
[38.]
A. Krivine, G. Firtion, L. Cao, C. Francoual, R. Henrion, P. Lebon.
HIV replication during the first weeks of life.
Lancet, 339 (1992), pp. 1187-1189
[39.]
A.M. Duliege, A. Messiah, S. Blanche, M. Tardieu, C. Griscelli, A. Spira.
Natural history of human immunodeficiency virus type 1 infection in children: prognostic value of laboratory test on bimodal progression of the disease.
Pediatr Infect Dis J, 11 (1992), pp. 630-645
[40.]
P.A. Pizzo, C.M. Wilfert.
The Pediatric Aids Siena Workshop II. Markers and determinants of disease progression in children with HIV infection.
J Aids, 8 (1995), pp. 30-44
[41.]
M.J. Mayaux, M. Burgard, J.P. Teglas, J. Cottalorda, A. Krivine, F. Simon.
Neonatal characteristics in rapidly progressive perinatally acquired HIV-1 disease.
Jama, 275 (1996), pp. 606-610
[42.]
G. Scarlatti.
Paediatric HIV infection.
[43.]
L.T. Spencer, M.T. Ogino, W.M. Danker, S.A. Spector.
Clinical significance of human immunodeficiency virus type 1 phenotypes in infected children.
J Infect Dis, 169 (1994), pp. 491-495
[44.]
M. Koot, I.P. Keet, A.H. Vos, De Goedere, M.T. Roos, R.A. Coutinho.
Prognostic value of HIV-1 biologicalal phenotype for rate of CD4+ count cell depletion and progression to Aids.
Ann Intern Med, 118 (1993), pp. 681-688
[45.]
M.A. Muñoz-Fernández, J. Navarro, R.A. Obregón, Arias, M.D. Gurbindo, T.H. Sampelayo.
Immunological and virological markers of disease progression in HIV-1 infected children.
Acta Paediatr, 421 (1997), pp. 46-51
[46.]
C. Balotta, M.C. Colombo, G. Colucci, A. Vigano, C. Riva, L. Papagno.
Plasma viremia and virus phenotype are correlates of disease progression in vertically human immunodeficiency virus type 1-infected children.
Pediatr Infect Dis J, 16 (1997), pp. 205-211
[47.]
S. Blanche, F. Veber, C. Griscelli.
Berrebi, (1988),
[48.]
Italian Multicentry study. Epidemiology, clinical features and prognostic factors of pediatric HIV infection.
Lancet, 2 (1988), pp. 1043-1046
[49.]
S. Blanches, M. Newell, M. Mayaux, A.T. Dunn, J.P. Teglas, C. Rouzioux.
Morbidity and mortality in European Children vertically infected by HIV-1: The French prospective study and the European collaborative study.
J Acquir Immune Def Syndrome, 14 (1997), pp. 1442-1450
[50.]
M.F. Rogers, C.Y. Ou, B. Kilbourne, G. Schochetman.
Advances and problems in the diagnosis of human immunodeficiency virus infection in infants.
Pediatr Infect Dis, 10 (1991), pp. 523-531
[51.]
G.B. Scott, C. Hutto, R.W. Makuch.
Survival in children perinatally acquired human immunodeficiency virus type 1 infection.
N Engl J Med, 321 (1989), pp. 1791-1796
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