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HLA-B*5701 screening for hypersensitivity to Abacavir

Mallal, S., Phillips, E., Carosi, G., Molina, J-M, Workman, C., Tomazic, J., Jagel-Guedes, E., Rugina, S., Kozyrev, O., Cid, J.F., Hay, P., Nolan, D., Hughes, S., Hughes, A., Ryan, S., Fitch, N., Thorborn, D. and Benbow, A. (2008) HLA-B*5701 screening for hypersensitivity to Abacavir. The New England Journal of Medicine, 358 (6). pp. 568-579.

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    Link to Published Version: http://www.nejm.org/doi/full/10.1056/NEJMoa0706135
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    Abstract

    Background
    Hypersensitivity reaction to abacavir is strongly associated with the presence of the HLA-B*5701 allele. This study was designed to establish the effectiveness of prospective HLA-B*5701 screening to prevent the hypersensitivity reaction to abacavir.

    Methods
    This double-blind, prospective, randomized study involved 1956 patients from 19 countries, who were infected with human immunodeficiency virus type 1 and who had not previously received abacavir. We randomly assigned patients to undergo prospective HLA-B*5701 screening, with exclusion of HLA-B*5701–positive patients from abacavir treatment (prospective-screening group), or to undergo a standard-of-care approach of abacavir use without prospective HLA-B*5701 screening (control group). All patients who started abacavir were observed for 6 weeks. To immunologically confirm, and enhance the specificity of, the clinical diagnosis of hypersensitivity reaction to abacavir, we performed epicutaneous patch testing with the use of abacavir.

    Results
    The prevalence of HLA-B*5701 was 5.6% (109 of 1956 patients). Of the patients receiving abacavir, 72% were men, 84% were white, and 18% had not previously received antiretroviral therapy. Screening eliminated immunologically confirmed hypersensitivity reaction (0% in the prospective-screening group vs. 2.7% in the control group, P<0.001), with a negative predictive value of 100% and a positive predictive value of 47.9%. Hypersensitivity reaction was clinically diagnosed in 93 patients, with a significantly lower incidence in the prospective-screening group (3.4%) than in the control group (7.8%) (P<0.001).

    Conclusions
    HLA-B*5701 screening reduced the risk of hypersensitivity reaction to abacavir. In predominantly white populations, similar to the one in this study, 94% of patients do not carry the HLA-B*5701 allele and are at low risk for hypersensitivity reaction to abacavir. Our results show that a pharmacogenetic test can be used to prevent a specific toxic effect of a drug.

    Publication Type: Journal Article
    Murdoch Affiliation: Institute for Immunology and Infectious Diseases
    Publisher: Massachusetts Medical Society
    Copyright: © 2008 Massachusetts Medical Society
    URI: http://researchrepository.murdoch.edu.au/id/eprint/8930
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