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. 
(ClinicalTrials.gov number, NCT00340080.)