HLA and drug-induced toxicity.
The discovery of new associations between drug toxicities and specific HLA alleles has been facilitated by the use of DNA-based molecular techniques and the introduction of higher-resolution HLA typing, which have replaced serological typing in this field of study. Drug toxicity/HLA associations have been best documented for immunologically mediated reactions, such as drug hypersensitivity reactions associated with the use of abacavir, and severe cutaneous adverse drug reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis induced by carbamazepine and allopurinol use, respectively. The implementation of HLA-B*5701 screening for the prevention of abacavir hypersensitivity syndrome (ABC HSR) has provided a model approach that can be applied to the screening of other drugs. High-level clinical evidence supporting HLA-B*5701 screening for ABC HSR has converged with experimental findings characterizing the CD8+T-cell HLA-B*5701-restricted immune response triggered by abacavir. This has been followed by the successful development of simplified inexpensive and quality-assured laboratory tests for HLA-B*5701 and ongoing quality assurance programs, resulting in a paradigm both for the implementation of HLA-B*5701 screening for HIV providers as well as for the broader successful implementation of pharmacogenetic screening in the clinic.
Phillips
Elizabeth J
EJ
Royal Perth Hospital and PathWest, Department of Clinical Immunology and Immunogenetics, Western Australia, Australia. e.phillips@iiid.com.au
Mallal
Simon A
SA
D015224:Dideoxynucleosides / Q000009:adverse effects; D004342:Drug Hypersensitivity / Q000276:immunology*; D005820:Genetic Testing; D015658:HIV Infections / Q000175:diagnosis / Q000821:virology; D006649:Histocompatibility Antigens / Q000276:immunology*; D006801:Humans; D010597:Pharmacogenetics; D000099227:Abacavir
D015224:Dideoxynucleosides; D006649:Histocompatibility Antigens; D000099227:Abacavir