Abacavir hypersensitivity syndrome (AHS) is a potentially life-threatening 
illness occurring in 4-8% of those initiating the drug. Early studies identified 
a strong association between the MHC class I allele HLA-B*5701 and AHS. These 
studies suggested that HLA-B*5701 holds promise as a screening test to prevent 
AHS, but concern arose from HLA-B*5701-negative cases with a clinical diagnosis 
of AHS, and particularly from early reports of apparently low sensitivities of 
HLA-B*5701 for AHS in patients of non-White race. However, open screening 
studies suggested that HLA-B*5701 screening can largely eliminate AHS. 
Furthermore, skin-patch testing was used in later-generation studies to separate 
those patients with true immunologically mediated AHS from those with 
false-positive clinical diagnoses. Currently, high-level evidence suggests that 
HLA-B*5701 has a negative predictive value of 100% for patch-test-confirmed AHS, 
which is generalizable across White and Black populations. Current HIV treatment 
guidelines have been revised to reflect the recommendation that HLA-B*5701 
screening be incorporated into routine care for patients who may require 
abacavir. New laboratory techniques such as PCR and flow cytometric methods, as 
well as an international quality assurance program, have evolved to ensure the 
availability of cost-effective screening methods whose consistency and standard 
can be maintained over time. An elegant body of basic science has evolved, which 
supports and complements the clinical research in suggesting that AHS is 
specifically and exquisitely restricted by HLA-B*5701 and mediated by CD8+ 
lymphocytes. Abrogating factors explaining why 45% of those carrying HLA-B*5701 
can tolerate abacavir remain to be defined. The research approach applied to AHS 
has led to a genetic screening test being successfully implemented globally in 
primary HIV clinical practice. The abacavir 'example' can be applied to other 
drugs to facilitate the development and operationalization of genetic tests that 
may be useful to predict and prevent otherwise unpredictable drug reactions.