Journal Information
Vol. 33. Issue 3.
Pages 155-160 (January 2009)
Vol. 33. Issue 3.
Pages 155-160 (January 2009)
Full text access
Correlation, in previously treated HIV-1 positive patients, between hypersensitivity reaction to abacavir and the presence of the HLA-B*5701 allele
Correlación, en pacientes infectados por el VIH-1 y previamente tratados, entre la reacción de hipersensibilidad a abacavir y el alelo HLA-B*5701
Visits
1785
Noemí Pérez Priora,
Corresponding author
nopepri@hotmail.com

Corresponding author.
, Amparo Rocher Millaa, Enrique Soler Companyb, Juan Flores Cidc, Benjamín Sarria Chustd
a Servicio de Farmacia, Hospital Arnau de Vilanova, Valencia, Spain
b Departamento de Farmacología en la Universidad de Valencia, Servicio de Farmacia, Hospital Arnau de Vilanova, Valencia, Spain
c Medicina Interna-Unidad de Enfermedades Infecciosas, Hospital Arnau de Vilanova, Valencia, Spain
d Departamento de Farmacología, Universidad de Valencia, Valencia, Spain
This item has received
Article information
Abstract
Introduction

Hypersensitivity reaction to abacavir (a powerful inverse transcriptase inhibitor) is a serious adverse effect that limits its use in antiretroviral treatment and requires a high level of clinical surveillance. Certain haplotypes of the primary histocompatibility complex proteins (HLA-B*5701) are very significant predictors of the risk of hypersensitivity to this drug. The purpose of this study is to identify the cases where a probable hypersensitivity reaction to abacavir presented the HLA-B*5701 allele.

Method

A retrospective study was conducted in all HIV-1 positive adult patients infected treated with abacavir between January 2000 and December 2007, in Department 6 of the Agencia Valenciana de Salud (Valencia Health Agency). The adverse effects developed by the patients were collected to determine which cases presented a probable clinically diagnosed hypersensitivity reaction. Finally, these 39 patients were screened for HLA-B*5701.

Results

In total, 323 patients were treated with abacavir between 2000 and 2007. The treatment was discontinued in 12.1% (n=39 patients) presenting a hypersensitivity reaction. Nine (23.1%) of these were HLA-B*5701 positive. Eight patients presented skin rash and positivity was observed in only single patient with gastrointestinal symptoms and fever.

Conclusions

The administration of the HLA-B*5701 gene test may be of benefit in clinical practice, because it prevents diagnostic errors of the hypersensitivity reaction and enables more accurate interpretation of the symptoms.

Keywords:
Pharmacogenetics
Hypersensitivity reaction
Abacavir
HLA-B*5701
HIV-1
Resumen
Introducción

La reacción de hipersensibilidad a abacavir (un potente inhibidor de la transcriptasa inversa) es un efecto adverso importante que limita su uso en la terapia antirretroviral y precisa un elevado grado de vigilancia clínica. Determinados haplotipos de las proteínas del complejo principal de histocompatibilidad (HLA-B*5701) predicen, de forma muy significativa, el riesgo de hipersensibilidad a este fármaco. El objetivo del estudio es identificar los casos que, después de desarrollar una probable reacción de hipersensibilidad a abacavir, presentaban el alelo HLA-B*5701.

Métodos

Se ha realizado un estudio retrospectivo a todos los pacientes adultos infectados por el virus de la inmunodeficiencia humana 1 (VIH-1) que recibieron tratamiento con abacavir entre enero de 2000 y diciembre de 2007, en el Departamento 6 de la Agencia Valenciana de Salud. Se recogieron los efectos adversos desarrollados por los pacientes para identificar los casos con probable reacción de hipersensibilidad diagnosticada clínicamente. Finalmente, se realizó la tipificación de HLA-B*5701 a estos 39 pacientes.

Resultados

En total, 323 pacientes recibieron tratamiento con abacavir entre 2000 y 2007. Se retiró el tratamiento por reacción de hipersensibilidad a 39 pacientes (12,1%); 9 (23,1%) de ellos resultaron HLA-B*5701 positivo; 8 pacientes manifestaron exantema y únicamente se observó positividad en un paciente con síntomas gastrointestinales y fiebre.

Conclusiones

La realización del test genético HLA-B*5701 podría ser favorable para la práctica clínica habitual, ya que evita errores en el diagnóstico de la reacción de hipersensibilidad y permite interpretar los síntomas con más seguridad.

Palabras clave:
Farmacogenética
Reacción de hipersensibilidad
Abacavir
HLA-B*5701
VIH-1
Full text is only available in PDF
References
[1.]
Panel de expertos de Gesida y PNS. Recomendaciones de Gesida/Plan Nacional sobre el Sida respecto al tratamiento antirretroviral en adultos infectados por el virus de la inmunodeficiencia humana [updated Jan 2008].
[2.]
S.M. Hammer, M.S. Saag, M. Schechter, J.S. Montaner, R.T. Schooley, D.M. Jacobsen, et al.
Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society-USA panel.
JAMA, 296 (2006), pp. 827-843
[3.]
D:A:D Study Group.
Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration.
Lancet-Published Online, (2008),
[4.]
J.H. Stein, J.S. Currier.
Risk of myocardial infarction and nucleoside analogues.
Lancet Published Online, (2008),
[5.]
P.J. Easterbrook, A. Waters, S. Murad, et al.
Epidemiological risk factors for hypersensitivity reactions to Abacavir.
HIV Med, 4 (2003), pp. 321-324
[6.]
Hernández JE, Cutrell A, Edwards M, et al. Clinical risk factors for hypersensitivity reactions to Abacavir: retrospective analysis of over 8000 subjects receiving abacavir in 34 clinical trials. Program and abstracts of the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, September 14-17, 2003. Washington, DC: American Society for Microbiology, 2003 [abstract 339].
[7.]
A.G. Cutrell, J.E. Hernandez, J.W. Fleming, et al.
Updated clinical risk factor analysis of suspected hypersensitivity reactions to abacavir.
Ann Pharmacother, 38 (2004), pp. 2171-2172
[8.]
C.A. Hughes, M.M. Foisy, N. Dewhurst, N. Higgins, L. Robinson, D.V. Kelly, et al.
Abacavir hypersensitivity reaction: an update.
Ann Pharmacother, 42 (2008), pp. 387-396
[9.]
Complete sequence and gene map of a human major histocompatibility complex. The MHC sequencing consortium.
Nature, 401 (1999), pp. 921-923
[10.]
S. Mallal, E. Phillips, G. Carosi, et al.
HLA-B*5701 screening for hypersensitivity to abacavir.
N Engl J Med, 358 (2008), pp. 568-579
[11.]
E.J. Phillips, G.A. Wong, R. Kaul, et al.
Clinical and immunogenetic correlates of abacavir hypersensitivity.
AIDS, 19 (2005), pp. 979-981
[12.]
S. Mallal, D. Notan, C. Witt, 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
[13.]
A.M. Martin, D. Nolan, S. Gaudieri, 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
[14.]
S. Hetherington, A.R. Hughes, M. Mosteller, et al.
Genetic variations in HLA-B region and hypersensitivity reactions to abacavir.
Lancet, 35 (2002), pp. 1121-1122
[15.]
M. Saag, R. Balu, E. Phillips, P. Brachman, C. Martorell, W. Burman, et al.
High sensitivity of human leukocyte antigen-b*5701 as a marker for immunologically confirmed abacavir hypersensitivity in white and black patients.
Clin Infect Dis, 46 (2008), pp. 1111-1118
[16.]
P.G. Clay.
The abacavir hypersensitivity reaction: a review.
Clin Ther, 24 (2002), pp. 1502-1514
[17.]
R.G. Hewitt.
Abacavir hypersensitivity reaction.
Clin Infect Dis, 34 (2002), pp. 1137-1142
[18.]
H. Peyriere, V. Guillemin, A. Lotthe, et al.
Reasons for early abacavir discontinuation in HIV-infected patients.
Ann Pharmacother, 37 (2003), pp. 1392-1397
[19.]
S. Hetherington, S. McGuirk, G. Powell.
Hipersensitivity reactions during therapy with the nucleoside reverse transcriptase inhibitor abacavir.
Clin Ther, 23 (2001), pp. 1603-1614
[20.]
A.R. Hughes, M. Mosteller, A.T. Bansal, et al.
Association of genetic variations in HLA-B region with hypersensitivity to abacavir in some, but not all, populations.
Pharmacogenetics, 5 (2004), pp. 203-211
[21.]
N. Tesch, M. Vogel, J.C. Wasmuth, et al.
Abacavir-associated drug hypersensitivity is strongly associated with the human leukocyte antigen B-57 allele.
Programs and abstracts of the 8th International Congress on Drug Therapy in HIV Infecction, Glasgow, Scotland, November 12–16,
[22.]
D. Nolan, S. Gaudieri, S. Mallal.
Pharmacogenetics: a practical role in predicting antiretroviral drug toxicity?.
J HIV Ther, 8 (2003), pp. 36-41
[23.]
J.S. Lambert, M. Seidlin, R.C. Reichman, et al.
2′,3′-dideoxyinosine (ddI) in patients with the acquired inmunodeficincy syndrome or AIDS-related complex. A phase I trial.
N Engl J Med, 322 (1990), pp. 1333-1340
[24.]
G.K. Robbins, G.V. De, R.W. Shafer, et al.
Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection.
N Engl J Med, 349 (2003), pp. 2293-2303
[25.]
R. Levy, D. Labriola, N. Ruiz.
Low two-year risk of virologic failure with first regimen HAART.
8th Conference on Retroviruses and Opportunistic Infections, Chicago, 4–8 February,
[26.]
E.J. Phillips, G.A. Wong, R. Kaul, et al.
Clinical and immunogenetic correlates of abacavir hypersensitivity.
AIDS, 19 (2005), pp. 979-981
[27.]
W. Symonds, A. Cutrell, M. Edwards, et al.
Risk factor analysis of hypersensitivity reactions to abacavir.
Clin Ther, 24 (2002), pp. 565-573
[28.]
D. Chessman, T. Lethborg, L. Kostenko, et al.
Abacavir hypersensitivity in HLA-B57-positive individuals with HIV infection is dependent upon the conventional MHC-I Ag presentation path-way.
Tissue Antigens, 69 (2007), pp. 373
[29.]
D. Hughes, F. Vilar, C. Ward, A. Alfirevic, B. Park, M. Pirmohamed.
Cost-effectiveness analysis of HLA B*5701 genotyping in preventing abacavir hypersensibility.
Pharmacogenetics, 14 (2004), pp. 335-342
Copyright © 2009. Sociedad Española de Farmacia Hospitalaria
Download PDF
Idiomas
Farmacia Hospitalaria
Article options
Tools
es en

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

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

es en
Política de cookies Cookies policy
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here.