title: Pharmacogenetics of antiretroviral therapy: genetic variation of response and toxicity.
abstract: The application of a pharmacogenetic approach to antiretroviral drug therapy represents a significant challenge, as treatment involves multiple drugs and drug classes with the potential for significant variability in drug-host, as well as drug-drug, interactions. However, despite this inherent complexity, considerable gains have been made in understanding how genetic factors influence the efficacy and toxicity of HIV therapy. In this review the available evidence regarding genetic variation in drug disposition will be examined, including the potential for relatively polymorphic drug-metabolizing enzymes (e.g., cytochrome P450 isoforms) and drug transporters (e.g., P-glycoprotein) to influence the disposition of HIV protease inhibitor and non-nucleoside reverse transcriptase inhibitor drugs. In addition, the role of genetic variation in determining the immune response to drug-specific antigens will be considered as a potentially significant determinant of susceptibility to idiosyncratic drug reactions (e.g., major histocompatibility complex alleles associated with abacavir hypersensitivity). The current and potential clinical utility of pharmacogenetic testing in HIV management will also be emphasized.
authors.affiliation: Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, Western Australia.
authors.forename: Annalise M
authors.initials: AM
authors.lastname: Martin
authors.forename: David
authors.initials: D
authors.lastname: Nolan
authors.forename: Silvana
authors.initials: S
authors.lastname: Gaudieri
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Phillips
authors.forename: Simon
authors.initials: S
authors.lastname: Mallal
mesh_terms: D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001692:Biological Transport / Q000235:genetics; D004342:Drug Hypersensitivity / Q000209:etiology / Q000235:genetics; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced / Q000235:genetics; D006801:Humans; D010597:Pharmacogenetics; D014018:Tissue Distribution
chemical_list: D044966:Anti-Retroviral Agents