Article information
En los últimos años se han producido grandes avances en la atención de los niños con infección por el virus de la inmunodeficiencia humana (VIH), sobre todo en el tratamiento antirretroviral, que se ha traducido en un aumento en la supervivencia y en la calidad de vida. El objetivo que se pretende con el tratamiento antirretroviral de gran actividad (TARGA), consistente en la combinación de al menos tres fármacos potentes, es la máxima y más duradera supresión de la replicación viral, lo cual no siempre es posible, a pesar de lo cual existe una mejoría inmunológica y clínica franca. Persisten grandes obstáculos para conseguir y mantener una máxima supresión de la replicación viral a largo plazo, entre los que se destacan la dificultad de adherencia permanente, con regímenes complejos y la posible toxicidad de la medicación. Los efectos adversos del tratamiento son frecuentes, siendo preocupante la elevada prevalencia de complicaciones metabólicas con unas consecuencias futuras desconocidas. Estas dificultades están motivando una tendencia actual para el inicio del tratamiento más conservadora, así como la implementación de estrategias con opciones terapéuticas simplificadas y con menor toxicidad. Es necesario continuar el desarrollo de fármacos que permitan vencer las todavía importantes limitaciones del tratamiento antirretroviral actual.
Palabras clave:
Infección por el VIH
Niños
Tratamiento antirretroviral
In recent years, major advances have been made in the care of HIV-infected children, particularly in antiretroviral treatment, which have dramatically improved survival and quality of life. The goal of highly active antiretroviral therapy (HAART), which includes at least three potent drugs, is the maximal and most durable suppression of viral replication possible, which is often not achieved despite clear immunologic and clinical improvement. There are still major barriers to achieving this goal, mainly the difficulty of permanent adherence to complex regimens and treatment-related toxicities. Adverse events are frequent, including a high prevalence of metabolic complications with unknown consequences in the future. These drawbacks of antiretroviral treatment are leading to a more conservative initial approach, as well as to research into simpler and less toxic therapeutic options. New strategies should continue to be developed to overcome the still important limitations of current antiretroviral treatment.
Key words:
HIV infection
Children
Antiretroviral treatment
Full text is only aviable in PDF
Bibliografía
[1]
J.T. Ramos, J. Saavedra Lozano, M.I. De José.
Tratamiento de la infección por VIH en la infancia.
An Esp Pediatr, 99 (1998), pp. 222-237
[2]
UNAIDS/WHO Working Group on Global HIV/AIDS and STD Surveillance. Report on the Global HIV/AIDS Epidemic. Estimación en Diciembre 2002 Ginebra: World Health Organization, 2002. Disponible en: http://www.unaids.org.
[3]
J.A. Iribarren, J.T. Ramos, L. Guerra, O. Coll, P. Domingo, M.I. De José, et al.
Prevención de la transmisión vertical y tratamiento de la infección por el virus de la inmunodeficiencia humana en la mujer embarazada.
Enf Inf Microb Clin, 19 (2001), pp. 314-335
[4]
J.T. Ramos, J. Ruiz-Contreras, R. Bastero, C. Barrios, P. Moreno, R. Delgado.
Efectividad de la zidovudina en la reducción de la transmisión vertical del VIH.
Med Clin (Barc), 113 (2000), pp. 245-252
[5]
Ministerio de Sanidad y Consumo. Vigilancia del SIDA en España. Actualización 31 Diciembre de 2002. Disponible en http//www.msc.es.
[6]
S. Gortmaker, M. Hughes, R. Oyomopito, M. Brady, G.M. Johnson, G.R. Seage, et al.
Impact of introduction of protease inhibitor therapy on reductions in mortality among children and youth infected with HIV-1.
N Engl J Med, 345 (2001), pp. 1522-1528
[7]
M.M. De Martino, P.A. Tovo, M. Balducci, L. Galli, C. Gabiano, G. Rezza, et al.
Reduction in mortality with availability of antiretroviral therapy for children with perinatal HIV-1 infection.
JAMA, 284 (2000), pp. 190-197
[8]
J. Sánchez-Granados, J.T. Ramos, M.I. González-Tomé, P. Rojo, S. Fernández de Miguel, P. Ferrando, et al.
Impact of HAART on the survival and disease progression in HIV-1 infected children.
Pediatr Infect Dis J, 22 (2003), pp. 863-867
[9]
D.M. Gibb, A. Newberry, N. Klein, A. De Rossi, I. Grosch-Woerner, A. Babiker.
Immune repopulation after HAART in previously untreated HIV-infected children.
Lancet, 355 (2000), pp. 1331-1332
[10]
J.T. Ramos, P. Rojo, S. Guillén.
Tratamiento antirretroviral en la infancia.
Infección por VIH/SIDA. Avances en la optimización del tratamiento, 1.a, pp. 69-82
[11]
R.B. Van Dike, S. Lee, G.M. Jonhson, A. Wiznia, K. Mohan, K. Stanley, et al.
Reported adherence as a determinant of response to highly active antiretroviral therapy in children who have human immunodeficiency virus infection.
Pediatrics, 109 (2002), pp. e61
[12]
E.G. Leonard, G.A. McComsey.
Metabolic complications of antiretroviral therapy in children.
Pediatr Infect Dis J, 22 (2003), pp. 77-84
[13]
D.C. Watson, J.J. Farley.
Efficacy and adherence to highly active antiretroviral therapy (HAART) in children infected with human immunodeficiency virus type 1.
Pediatr Infect Dis J, 18 (1999), pp. 682-689
[14]
D.M. Gibb, R.L. Goodall, V. Giacomet, L. McGee, A. Compagnucci, H. Lyall.
for the PENTA Steering Committee. Adherence to prescribed antiretroviral therapy in with human immunodeficiency virus infected children.
Pediatr Infect Dis J, 22 (2003), pp. 56-62
[15]
M. Sharland, G. Castelli, J.T. Ramos, S. Blanche, D. Gibb.
on behalf of the PENTA steering committee. PENTA (Pediatric European Network for Treatment of AIDS). European guidelines of antiretroviral treatment of HIV-infected children.
HIV Medicine, 3 (2002), pp. 215-226
[16]
M.J. Mellado, R. González Montero.
Terapia antirretroviral y efectos adversos en pediatría.
Infección por VIH en pediatría. Biblioteca del SIDA, 1.a, pp. 33-48
[17]
X. Sáez-Llorens, A. Violari, C.O. Deetz, R. Rode, P. Gómez, E. Handelsman, et al.
Forty-eight-week evaluation of lopinavir/ritonavir, a new protease inhibitor, in human immunodeficiency virus infected children.
Pediatr Infect Dis J, 22 (2003), pp. 216-223
[18]
J.A. Church, W.G. Mitchell, I. González-Gómez, J. Christensen, T.H. Vu, S. Dimauro, et al.
Mitochondrial DNA depletion, near-fatal metabolic acidosis, and liver failure in an HIV-infected child treated with combination antiretroviral therapy.
J Pediatr, 138 (2001), pp. 748-751
[19]
S. Arpadi, P. Cuff, M. Horlick, J. Wang, D.P. Kotler.
Lypodystrophy in HIV-infected children is associated with high viral load and low CD4-lymphocyte count and CD4-lymphocyte percentage and baseline and use of protease inhibitors and stavudine.
J Acquir Immun Def Syndr, 27 (2001), pp. 30-34
[20]
P. Brambilla, D. Bricalli, N. Sala, F. Renzetti, P. Manzoni, A. Vanzulli, et al.
Highly active antiretroviral-treated HIV-infected children show fat distribution changes even in the absence of clinical evidence of lipodystrophy.
AIDS, 15 (2001), pp. 2415-2422
[21]
D. Jaquet, M. Lévine, E. Ortega-Rodríguez, A. Faye, M. Polak, E. Vilmer, et al.
Clinical and metabolic presentation of the lipodystrophic syndrome in HIV-infected children.
AIDS, 14 (2000), pp. 2123-2128
[22]
R.A. Amaya, C.A. Koezinetz, A. McMeaans, H. Schwardwald, M.A. Kline.
Lipodystrophy syndrome in human immunodeficiency virus-infected children.
Pediatr Infect Dis J, 21 (2002), pp. 405-410
[23]
A. Vigano, S. Mora, C. Testolin, S. Beccio, L. Schneider, D. Bricalli, et al.
Increased lipodystrophy is associated with increased exposure to highly active antiretroviral theraphy in HIV-infected children.
J Acquir Immune Def Syndr, 32 (2003), pp. 482-489
[24]
S. Arpadi, M. Horlick, J. Thornton, P.A. Cuff, J. Wang, D.P. Kotler.
Bone mineral content is lower in prepubertal HIV-infected children.
J Acquir Immune Def Syndr, 29 (2002), pp. 450-454
[25]
K. Miller, H. Masur, E.C. Jones, G.E. Joe, M.E. Rick, G.G. Kelly, et al.
High prevalence of osteonecrosis of the femoral head in HIV-infected adults.
Ann Intern Med, 137 (2002), pp. 17-24
[26]
D.M. Gaughan, L.M. Mofenson, M.D. Hughes, S. Seage, J. Oleske.
for the PACTG 219 Team. Avascular necrosis of the hip (Leggs- Calve-Perthes disease) in HIV-infected children in long-term follow-up: PACTG Study 219.
Pediatrics, 109 (2002), pp. 1-8
[27]
M. Schambelan, C.A. Benson, A. Carr, J.S. Currier, M.P. Dubé, J.G. Gerber, et al.
Management of metabolic complications associated with antiretroviral therapy for HIV-1 infection: Recommendations of an International AIDS Society-USA Panel.
J Acquir Immun Def Syndr, 31 (2002), pp. 257-275
[28]
P. Yeni, S. Hammer, C. Carpenter, D.A. Cooper, M.A. Fischl, J.M. Gatell, et al.
Antiretroviral treatment for adult with HIV infecction in 2002: Updated recommendations of the IAS-USA Panel.
JAMA, 288 (2002), pp. 222-235
[29]
Guidelines for the use of antiretroviral agents in pediatric HIV infection. Disponible en: http://www.hivatis.org. Acceso en Junio 2003.
[30]
L.M. Mofenson, J. Korelitz, W.A. Meyer, J. Bethel, K. Rich, S. Pahwa, et al.
The relationship between serum human immunodeficiency virus type 1 (HIV-1) RNA level. CD4 lymphocyte percent, and long-term mortality risk in HIV-1-infected children.
J Infect Dis, 175 (1997), pp. 1029-1038
[31]
HIV., Pediatric Prognostic Markers Collaborative Study Group.
Short-term disease progression in HIV-1 infected children receiving no antiretroviral therapy or zidovudine monotherapy: Estimates according to CD4 percent, viral load and age.
Lancet, 362 (2003), pp. 1605-1611
[32]
A. Faye, C. Bertone, J.P. Teglas, M.L. Chaix, G. Duard, D. Firtion, et al.
Early multitherapy including a protease inhibitor for human immunodeficiency virus type 1-infected infants.
Pediatr Infect Dis, 21 (2002), pp. 518-525
[33]
Z.A. Scott, E.G. Chadwick, L.L. Gibson, M.D. Catalina, M.M. McManus, R. Yogev, et al.
Infrequent detection of HIV-1-specific, but not cytomegalovirus-specific, CD8(+) T cell responses in young HIV-1-infected infants. Young infants lack HIV-specific CD8+ T cell response.
J Immunol, 167 (2001), pp. 7134-7140
[34]
M.I. De José, J.T. Ramos, S. Álvarez, M.A. Muñoz-Fernández.
Vertical transmission of HIV-1 variants to reverse transcriptase and protease inhibitors.
Arch Intern Med, 161 (2001), pp. 2738-2739
[35]
F.T. Saulsbury.
Resolution of organ specific complications of human immunodeficiency virus infection in children with use of highly active antiretroviral therapy.
Clin Infect Dis, 32 (2001), pp. 464-468
[36]
J.P. Phair, J.W. Mellors, R. Detels, J.B. Margolick, A. Muñoz.
Virologic and immunologic values allowing safe deferral of antiretroviral therapy.
AIDS, 16 (2002), pp. 2455-2459
[37]
Pediatric European Network for treatment of AIDS.
A 72 week follow-up of HAART started in infants aged less than 3 months: CD4, viral load and drug resistance in the PENTA 7 study.
AIDS, (2004),
[38]
C. Litalien, A. Faye, Jacqz-Aigrain, A. Compagnucci, C. Giaquinto, L. Harper, et al.
Pharmacokinetics of nelfinavir and its active metabolite, hydroxy-tert-butylamide, in infants perinatally infected with human immunodeficiency virus.
Pediatr Infect Dis, 22 (2003), pp. 48-55
[39]
E.G.H. Lyall, S. Head, M.D.S. Walters, G. Tudor-Williams.
for the Family HIV-team. Baby cocktail! – a palatable four drug combo for HIV infected infants.
AIDS, 14 (2000), pp. S77
[40]
J.T. Ramos, J.M. Sánchez-Granados, M.I. Gónzález Tomé.
Infección por VIH en pediatría.
Avances en la prevención y tratamiento de la infección VIH en el niño, 1.a, pp. 181-208
[41]
PENTA News. Pediatric European Network for the Treatment of AIDS. Disponible en: www.ctu.mrc.ac.uk/penta.
[42]
G. Verweel, M. Sharland, H. Lyall, V. Novelli, D. Gibb, G. Dumont, et al.
Nevirapine use in HIV-1 infected children.
AIDS, 17 (2003), pp. 1639-1647
[43]
S.E. Starr, C.A. Fletcher, S.A. Spector, F.H. Yong, T. Fenton, R.C. Brundage, et al.
Combination therapy with efavirenz, nelfinavir and nucleoside reverse-transcriptase inhibitors children infected with human immunodeficiency virus type-1.
N Engl J Med, 341 (1999), pp. 1874-1881
[44]
Pediatric European Network for treatment of AIDS.
A randomized trial evaluating 3 NRTI regimens with and without nelfinavir in previously untreted HIV-infected children: 48 week follow-up from the PENTA 5 trial.
Lancet, 359 (2002), pp. 733-740
[45]
S. Moreno.
Criterios para la elección del tratamiento antirretroviral.
Infección por VIH/SIDA. Avances en la optimización del tratamiento, 1.a, pp. 39-82
[46]
S. Staszewski, P. Keiser, J. Montaner, Raffi, J. Gathe, V. Brotas, et al.
Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral-naive HIV-infected adults: A randomized equivalence trial.
JAMA, 285 (2001), pp. 1155-1163
[47]
S. Walmsley, B. Bernstein, M. King, J. Arribas, G. Beall, P. Ruane, et al.
Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection.
N Engl J Med, 346 (2002), pp. 2039-2046
[48]
R.T. Schooley, P. Ruane, R.A. Myers, G. Beall, H. Lampiris, D. Berger, et al.
Tenofovir DF in antiretroviral-experienced patients: Results from a 48 week ramdomized, double blind study.
AIDS, 16 (2002), pp. 1257-1263
[49]
J.M. Molina, F. Ferchal, C. Rancinan, F. Raffi, W. Rozenbaum, D. Sereni, et al.
Once-daily combination therapy with emtricitabine, didanosine, and efavirenz in human immunodeficiency virusinfected patients.
J Infect Dis, 183 (2001 15), pp. 1539-1540
[50]
R. Rubio, M. Torralba.
Nuevos fármacos antirretrovirales.
Avances en la prevención y tratamiento de la infección VIH en el niño, 1.a, pp. 143-159
[51]
J. Martínez-Picado, A.V. Saavara, L. Sutton, R.T. D’Aquila.
Replicative fitness of protease inhibitor-resistant mutants of human immunodeficiency virus type 1.
J Virol, 73 (1999), pp. 3744-3752
[52]
F. Hoffmann, G. Notheis, U. Wintergerst, J. Eberle, L. Gütlern, B.H. Belohradsky.
Comparison of ritonavir plus saquinavir and nelfinavir plus saquinavir-containing regimens as salvage therapy in children with human immunodeficiency type 1 infection.
Pediatr Infect Dis J, 19 (2000), pp. 47-51
[53]
J. Durant, P. Clevenberg, P. Halfon, P. Delgiudice, S. Porsin, P. Simonet, et al.
Drug-resistance genotyping in HIV-1 therapy: The VIRADAPT randomized controlled trial.
Lancet, 353 (1999), pp. 2195-2199
[54]
G.L. Plosker, D.P. Figgitt.
Tipranavir. Drugs, 63 (2003), pp. 1611-1618
[56]
J.T. Ramos, P. Carreño.
Avances en la prevención y tratamiento en transmisión vertical del VIH.
SIDA. Hacia un tratamiento integral, 1.a, pp. 49-64
Copyright © 2004. Asociación Española de Pediatría
