• Simon Mallal, Elizabeth Phillips, Giampiero Carosi, Jean-Michel Molina, Cassy Workman, Janez Tomazic, Eva Jägel-Guedes, Sorin Rugina, Oleg Kozyrev, Juan Flores Cid, Phillip Hay, David Nolan, Sara Hughes, Arlene Hughes, Susanna Ryan, Nicholas Fitch, Daren Thorborn, Alastair Benbow, and PREDICT-1 Study Team.
• Royal Perth Hospital and Murdoch University, Perth, Australia. s.mallal@murdoch.edu.au
• N. Engl. J. Med. 2008 Feb 7; 358 (6): 568579568-79.

BackgroundHypersensitivity 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.MethodsThis 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.ResultsThe 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).ConclusionsHLA-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. (ClinicalTrials.gov number, NCT00340080.)Copyright 2008 Massachusetts Medical Society.

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