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La reacción de hipersensibilidad al abacavir (ABC) es un efecto adverso que se produce entre el 5 y el 8% de aquellas personas que inician el tratamiento con este fármaco y que limita el tratamiento en el futuro. Algunos factores genéticos del huésped, en especial el alelo HLA-B* 5701, se han identificado como factores de riesgo para desarrollar la reacción de hipersensibilidad en la raza caucásica. Por esta razón se plantea la posibilidad de implementar en la práctica habitual un test genético que permita detectar la presencia de este alelo con la finalidad de conseguir un perfil terapéutico personalizado. En este capítulo se documenta toda la información relacionada con la hipersensibilidad al ABC y sus marcadores genéticos e inmunológicos, las distintas técnicas para la detección del alelo HLA-B*5701, así como un resumen de los diferentes estudios realizados en el momento en distintas poblaciones.
Palabras clave:
Hipersensibilidad
HLA
HLA-B*5701
Abacavir
Hypersensitivity reactions to abacavir occur in 5-8% of patients starting treatment with this drug and limits future treatment. Some host genetic factors, especially the HLA-B* 5701 allele, have been identified as risk factors for hypersensitivity reaction in Caucasians. Consequently, the possibility of routine implementation of a genetic test to rule out the presence of this allele has been proposed to achieve a personalized therapeutic profile. The present article discusses all the information related to hypersensitivity to abacavir and its genetic and immunological markers, as well as the distinct techniques for HLA-B*5701 allele detection. The various studies performed to date in distinct population are also discussed.
Key words:
Hypersensitivity
HLA
HLA-B*5701
Abacavir
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Bibliografía
[1.]
R.G. Hewitt.
Abacavir hypersensitivity reaction.
Clin Infect Dis, 8 (2002), pp. 1137-1142
[2.]
H. Peyriere, V. Guillemin, A. Lotthe, V. Baillat, J. Fabre, C. Favier, et al.
Reasons for early abacavir discontinuation in HIV-infected patients.
Ann Pharmacother, 37 (2003), pp. 1392-1397
[3.]
S. Hetherington, S. McGuirk, G. Powell, A. Cutrell, O. Naderer, B. Spreen, et al.
Hypersensitivity reactions during therapy with the nucleoside reverse transcriptase inhibitor abacavir.
Clin Ther, 23 (2001), pp. 1603-1614
[4.]
L. Escaut, J.Y. Liotier, E. Albengres, N. Cheminot, D. Vittecoq.
Abacavir rechallenge has to be avoided in case of hypersensitivity reaction.
AIDS, 13 (1999), pp. 1419-1420
[5.]
H. Peyrieère, J. Nicolas, M. Siffert, P. Demoly, D. Hillaire-Buys, J. Reynes.
Hypersensitivity related to abacavir in two members of a family.
Ann Pharmacother, 35 (2001), pp. 1291-1292
[6.]
W. Symonds, A. Cutrell, M. Edwards, H. Steel, B. Spreen, G. Powell, et al.
Risk factor analysis of hypersensitivity reactions to abacavir.
Clin Ther, 24 (2002), pp. 565-573
[7.]
E.J. Phillips, J.R. Sullivan, S.R. Knowles, N.H. Shear.
Utility of patch testing in patients with hypersensitivity syndromes associated with abacavir.
AIDS, 16 (2002), pp. 2223-2225
[8.]
Mallal S, Phillips E, Carosi G, et al. PREDICT-1: a novel randomised prospective study to determine the clinical utility of HLA-B*5701 screening to reduce abacavir hypersensitivity in HIV-1 infected subjects (study CNA106030). 4th IAS Conference on HIV Pathogenesis, Treatment, and Prevention. July 22-25, 2007. Sydney. Abstract WESS101.
[9.]
S. Mallal, D. Nolan, C. Witt, G. Masel, A.M. Martin, C. Moore, et al.
Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse transcriptase inhibitor abacavir.
Lancet, 359 (2002), pp. 727-732
[10.]
S. Hetherington, A.R. Hughes, M. Mosteller, D. Shortino, K.L. Baker, W. Spreen, et al.
Genetic variations in HLA-B region and hypersensitivity reactions to abacavir.
Lancet, 359 (2002), pp. 1121-1122
[11.]
A.M. Martin, D. Nolan, S. Gaudieri, C.A. Almeida, R. Nolan, I. James, et al.
Predisposition to abacavir hypersensitivity conferred by HLA-B*5701 and a haplotypic Hsp70-Hom variant.
Proc Natl Acad Sci U S A, 101 (2004), pp. 4180-4185
[12.]
A.R. Hughes, M. Mosteller, A.T. Bansal, K. Davies, S.A. Haneline, E.H. Lai, CNA30027 Study Team; CNA30032 Study Team, et al.
Association of genetic variations in HLA-B region with hypersensitivity to abacavir in some, but not all, populations.
Pharmacogenomics, 5 (2004), pp. 203-211
[13.]
D.A. Hughes, F.J. Vilar, C.C. Ward, A. Alfirevic, B.K. Park, M. Pirmohamed.
Costeffectiveness analysis of HLA B*5701 genotyping in preventing abacavir hypersensitivity.
Pharmacogenetics, 14 (2004), pp. 335-342
[14.]
A.M. Martin, D. Nolan, S. Mallal.
HLA-B*5701 typing by sequence-specific amplification: validation and comparison with sequence-based typing.
Tissue Antigens, 65 (2005), pp. 571-574
[15.]
D. Nolan, S. Gaudieri, S. Mallal.
Pharmacogenetics: a practical role in predicting antiretroviral drug toxicity?.
J HIV Ther, 8 (2003), pp. 36-41
[16.]
A.M. Martin, R. Krueger, C.A. Almeida, D. Nolan, E. Phillips, S. Mallal.
A sensitive and rapid alternative to HLA typing as a genetic screening test for abacavir hypersensitivity syndrome.
Pharmacogenet Genomics, 16 (2006), pp. 353-357
[17.]
J.R. Foster.
The functions of cytokines and their uses in toxicology.
Int J Exp Pathol, 82 (2001), pp. 171-192
[18.]
N. Aziz, P. Nishanian, J.M. Taylor, R.T. Mitsuyasu, J.M. Jacobson, B.J. Dezube, et al.
Stability of plasma levels of cytokines and soluble activation markers in patients with human immunodeficiency virus infection.
J Infect Dis, 179 (1999), pp. 843-848
[19.]
E.C. Breen, M. McDonald, J. Fan, J. Boscardin, J.L. Fahey.
Cytokine gene expression occurs more rapidly in stimulated peripheral blood mononuclear cells from human immunodeficiency virus-infected persons.
Clin Diagn Lab Immunol, 7 (2000), pp. 769-773
[20.]
J. Jason, L.K. Archibald, O.C. Nwanyanwu, M. Bell, R.J. Jensen, E. Gunter, et al.
The effects of iron deficiency on lymphocyte cytokine production and activation: preservation of hepatic iron but not at all cost.
Clin Exp Immunol, 126 (2001), pp. 466-473
[21.]
R.V. House.
Cytokine measurement techniques for assessing hypersensitivity.
Toxicology, 158 (2001), pp. 51-58
[22.]
M. Britschgi, S. von Greyerz, C. Burkhart, W.J. Pichler.
Molecular aspects of drug recognition by specific T cells.
Curr Drug Targets, 4 (2003), pp. 1-11
[23.]
A.M. Martin, D. Nolan, S. Gaudieri, E. Phillips, S. Mallal.
Pharmacogenetics of antiretroviral therapy: genetic variation of response and toxicity.
Pharmacogenomics, 5 (2004), pp. 643-655
[24.]
T. Manchanda, D. Hess, L. Dale, S.G. Ferguson, M.J. Rieder.
Haptenation of sulfonamide reactive metabolites to cellular proteins.
Mol Pharmacol, 62 (2002), pp. 1011-1026
[25.]
M.P. Zanni, B. Schnyder, S. von Greyerz, W.J. Pichler.
Involvement of T cells in drug-induced allergies.
Trends Pharmacol Sci, 19 (1998), pp. 308-310
[26.]
M. Pirmohamed, D.J. Naisbitt, F. Gordon, B.K. Park.
The danger hypothesis—potential role in idiosyncratic drug reactions.
Toxicology, 181-182 (2002), pp. 55-63
[27.]
F. Sallusto, A. Lanzavecchia, C.R. Mackay.
Chemokines and chemokine receptors in T-cell priming and Th1/Th2-mediated responses.
Immunol Today, 19 (1998), pp. 568-574
[28.]
D.J. Naisbitt, M. Britschgi, G. Wong, J. Farrell, J.P. Depta, D.W. Chadwick, et al.
Hypersensitivity reactions to carbamazepine: characterization of the specificity, phenotype, and cytokine profile of drug-specific T cell clones.
Mol Pharmacol, 63 (2003), pp. 732-741
[29.]
J. Parkin, B. Cohen.
An overview of the immune system.
Lancet, 357 (2001), pp. 1777-1789
[30.]
A.G. Jarnicki, P.G. Fallon.
T helper type-2 cytokine responses: potential therapeutic targets.
Curr Opin Pharmacol, 3 (2003), pp. 449-455
[31.]
H. Lebrec, S. Kerdine, I. Gaspard, M. Pallardy.
Th(1)/Th(2) responses to drugs.
Toxicology, 158 (2001), pp. 25-29
[32.]
D.R. Lucey, M. Clerici, G.M. Shearer.
Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases.
Clin Microbiol Rev, 9 (1996), pp. 532-562
[33.]
B. Spellberg, J.E. Edwards Jr.
Type 1/Type 2 immunity in infectious diseases.
Clin Infect Dis, 32 (2001), pp. 76-102
[34.]
H.F. Merk.
Diagnosis of drug hypersensitivity: lymphocyte transformation test and cytokines.
Toxicology, 209 (2005), pp. 217-220
[35.]
D. Mauri-Hellweg, F. Bettens, D. Mauri, C. Brander, T. Hunziker, W.J. Pichler.
Activation of drug-specific CD4+ and CD8+ T cells in individuals allergic to sulfonamides, phenytoin, and carbamazepine.
J Immunol, 155 (1995), pp. 462-472
[36.]
E. Padovan, S. von Greyerz, W.J. Pichler, H.U. Weltzien.
Antigen-dependent and -independent IFN-gamma modulation by penicillins.
J Immunol, 162 (1999), pp. 1171-1177
[37.]
I. Guest, B. Sokoluk, J. MacCrimmon, J. Uetrecht.
Examination of possible toxic and immune mechanisms of clozapine-induced agranulocytosis.
Toxicology, 131 (1998), pp. 53-65
[38.]
E.J. Phillips, G.A. Wong, R. Kaul, K. Shahabi, D.A. Nolan, S.R. Knowles, et al.
Clinical and immunogenetic correlates of abacavir hypersensitivity.
AIDS, 19 (2005), pp. 979-981
[39.]
E. Hammond, C.A. Almeida, C. Mamotte, D. Nolan, E. Phillips, T.A. Schollaardt, et al.
External quality assessment of HLA-B*5701 reporting: an international multicentre survey.
Antiviral Ther, 12 (2007), pp. 1027-1032
[40.]
P.J. Easterbrook, A. Waters, S. Murad, N. Ives, C. Taylor, D. King, et al.
Epidemiological risk factors for hypersensitivity reactions to abacavir.
HIV Med, 4 (2003), pp. 321-324
[41.]
A.G. Cutrell, J.E. Hernandez, J.W. Fleming, M.T. Edwards, M.A. Moore, C.H. Brothers, et al.
Updated clinical risk factor analysis of suspected hypersensitivity reactions to abacavir.
Ann Pharmacother, 38 (2004), pp. 2171-2172
[42.]
A. Rauch, D. Nolan, A. Martin, E. McKinnon, C. Almeida, S. Mallal.
Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV cohort study.
Clin Infect Dis, 43 (2006), pp. 99-102
[43.]
S.T. Sadiq, M. Pakianathan.
Uncertainties of routine HLA B*5701 testing in black African HIV cohorts in the UK.
Sex Transm Inf, 83 (2007), pp. 181-182
[44.]
K. Cao, A.M. Moormann, K.E. Lyke, C. Masaberg, O.P. Sumba, O.K. Doumbo, et al.
Differentiation between African populations is evidenced by the diversity of alleles and haplotypes of HLA class I loci.
Tissue Antigens, 63 (2004), pp. 293-325
[45.]
H. Faruki, U. Heine, T. Brown, R. Koester, M. Lai-Goldman.
HLA-B*5701 clinical testing: early experience in the United States.
Pharmacogenet Genomics, 17 (2007), pp. 857-860
[46.]
D. Zucman, P. Truchis, C. Majerholc, S. Stegman, S. Caillat-Zucman.
Prospective screening for human leukocyte antigen-B*5701 avoids abacavir hypersensitivity reaction in the ethnically mixed French HIV population.
J Acquir Immune Defic Syndr, 45 (2007), pp. 1-3
[47.]
S. Mallal, E. Phillips, G. Carosi, J.M. Molina, C. Workman, J. Tomazic, PREDICT-1 Study Team, et al.
HLA-B*5701 screening for hypersensitivity to abacavir.
N Engl J Med, 358 (2008), pp. 568-579
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