Información de la revista
Vol. 52. Núm. 2.
Páginas 138-147 (Febrero 2000)
Compartir
Compartir
Descargar PDF
Más opciones de artículo
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
5446
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.
Este artículo ha recibido
Información del artículo
Resumen
Bibliografía
Descargar PDF
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.

El Texto completo está disponible en PDF
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
Copyright © 2000. Asociación Española de Pediatría
Idiomas
Anales de Pediatría
Opciones de artículo
Herramientas
es en

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

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