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Conference
"Clinical Applications of Pharmacogenetics in HIV" Dr. Simon Mallal (biography) English - 2006-05-26 - 35 minutes
(25 slides)
Summary : Given on behalf of Dr. Elizabeth Phillips, Dr. Mallal presents pharmacogenetics and pharmacogenomics in clinical practice. Polymorphisms in both hosts and pathogens constitute a large challenge in therapy. Pathogenic adaptability, as seen in HIV, will shape the response to particular drug interventions. Similarly, the host genetic makeup will also affect the response to treatment. Drugs therefore help us elucidate these polymorphic backgrounds.
Pharmacogenetics refers to a clinical entity (phenotype) that is further characterized by genetics (genotype). Conversely, pharmacogenomics attempts to identify the genotype in order to predict the risk of developing a particular phenotype.
Pharmacogenetic and pharmacogenomic approaches in choosing an optimal antiretroviral regimen are exemplified in abacavir hypersensitivity reactions. Clinical diagnosis of abacavir hypersensitivity has been shown to yield false positives (CNA3005, CNA30024). This over diagnosis subsequently leads to prompt discontinuation of abacavir which incurs significant healthcare costs. A study by Dr. Phillips and colleagues (2005) demonstrated that disrupting treatment too early resulted in increased consultations with emergency physicians and/or specialists with higher costs for services. Furthermore, it took longer for these patients to achieve undetectable viral loads.
Studies show that abacavir hypersensitivity can be more accurately diagnosed with the patch test. Dr. Mallal reiterates the differences between pharmacogenetics and pharmacogenomics by pointing out that patch testing should be employed in abacavir sensitized individuals, therefore serving as a diagnostic test and not a predictive test.
Learning objectives : After viewing this presentation participants will be able to discuss:
- Pharmacogenetics versus pharmacogenomics;
- Pharmacogenetics and potential applications in HIV therapeutics;
- Benefits of patch testing in diagnosing abacavir hypersensitivity.
Annalise M. Martin, David Nolan, Silvana Gaudieri, Coral Ann Almeida, Richard Nolan, Ian James, Filipa Carvalho, Elizabeth Phillips, Frank T. Christiansen, Anthony W. Purcell, James McCluskey, and Simon Mallal. Predisposition to abacavir hypersensitivity conferred by HLA-B*5701 and a haplotypic Hsp70-Hom variant Proceedings of the National Academy of Sciences of the United States of America. 15 March 2004, 101(12), 4180-4185.
Simon Mallal. Host genetics unplugged: Removing the camouflage of viral adaptation. Current Opinion in HIV and AIDS. May 2006, 1(3), 218-219.
Elizabeth Phillips. The pharmacogenetics of antiretroviral therapy. Current Opinion in HIV and AIDS. May 2006, 1(3), 249-256.
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