Logo image
Back
HLA-B*5701 screening for hypersensitivity to Abacavir
Journal article   Open access   Peer reviewed

HLA-B*5701 screening for hypersensitivity to Abacavir

S. Mallal, E. Phillips, G. Carosi, J-M Molina, C. Workman, J. Tomazic, E. Jagel-Guedes, S. Rugina, O. Kozyrev, J.F. Cid, …
The New England Journal of Medicine, Vol.358(6), pp.568-579
2008
DOI: https://doi.org/10.1056/NEJMoa0706135
pdf
HLA-B5701_screening183.10 kBDownloadView
Open Access
url
Link to Published Version *Subscription may be requiredView

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.

Details

Metrics

821 File views/ downloads
211 Record Views
Logo image