Author/Editor		Mallal, Simon; Phillips, Elizabeth; Carosi, Gianpiero; Molina, Jean-Michel; Workman, Cassy; Tomažič, Janez; Jagel-Guedes, Eva; Rugina, Sorin; Kozyrev, Oleg; Cid, Juan Flores
Title		HLA-B*5701 screening for hypersensitivity to abacavir
Type		članek
Source		N Engl J Med
Vol. and No.		Letnik 358, št. 6
Publication year		2008
Volume		str. 568-79
Language		eng
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). Conclusion: 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. (Abstract truncated at 2000 characters)
Descriptors		GENETIC SCREENING PATCH TESTS ADULT AGED DIDEOXYNUCLEOSIDES DOUBLE-BLIND METHOD DRUG HYPERSENSITIVITY GENETIC MARKERS GENOTYPE HIV INFECTIONS HIV-1 HLA-B ANTIGENS REVERSE TRANSCRIPTASE INHIBITORS