Overcoming the barrier of clinical translation: The Abacavir example
Phillips, E.J. (2009) Overcoming the barrier of clinical translation: The Abacavir example. In: Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT) Conference 2009, 29 November - 2 December 2009, Sydney Convention Centre, Sydney.
The discovery of the association between major histocompatibility complex class I allele, HLA-B*5701 and a hypersensitivity syndrome associated with the antiretroviral nucleoside reverse transcriptase inhibitor abacavir, marked the beginning of a new era opening up the potential for traditionally unpredictable or type B adverse drug reactions to be both predicted and prevented through genetic screening. Abacavir has provided a real world example where the necessary steps from discovery to implementation into clinical practice have been accomplished and screening has become routine in much of the developed world. Key to the success of clinical implementation of HLA-B*5701 screening for abacavir was 1) the ability to specifically phenotype true immunologically mediated abacavir hypersensitivity with skin patch testing 2) the high negative predictive value of HLA-B*5701 validated in a randomized double blinded controlled trial 3) Generalisability of the association between HLA-B*5701 and abacavir hypersensitivity across ethnicity. 4) The availability of inexpensive, quality assured, and cost-effective laboratory methods. The abacavir example is illustrative of future opportunities in pharmacogenetics and provides a roadmap to overcoming the inevitable challenges involved in the translation from discovery to widespread clinical application.
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|Murdoch Affiliation:||Institute for Immunology and Infectious Diseases|
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