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Pharmacogenomics of antiretroviral therapy

Effective therapy for human immunodeficiency virus (HIV) infection requires long‐term administration of multiple antiretroviral drugs. This has markedly reduced morbidity and mortality due to AIDS, but drug toxicities often limit the success of treatment. Using candidate gene approaches, pharmacogenomic studies have begun to identify associations between host allelic variants and increased risk of adverse reactions to antiretroviral medications. Of note are associations between abacavir hypersensitivity reactions and specific HLA and hsp70‐hom genotypes, and between CYP2B6 polymorphisms, efavirenz pharmacokinetics, and central nervous system side effects. Pharmacogenomics also has the long‐term potential to reveal new drug targets. The observation that a naturally occurring, nonfunctional deletion mutant of the HIV receptor gene CCR5 protected against HIV infection and slowed disease progression encouraged the development of drugs that target CCR5. Pharmacogenomics promises to improve the lives of persons living with HIV by identifying new therapeutic targets and by fostering rational drug prescribing that optimizes efficacy while minimizing toxicity. Drug Dev. Res. 62:213–220, 2004. © 2004 Wiley‐Liss, Inc.