[Importance of pharmacogenetics in antiretroviral metabolism and drug-transporters].

Wide intra- and inter-subject variability in antiretroviral drug response is observed. Pharmacotherapy of HIV-infected patients is challenging considering the great numbers of co-morbidities increasing the risk of drug-drug interactions. Drug-metabolism enzymes and drug-transporters regulate drug access to the systemic circulation, target cells and sanctuary sites; these factors determine pharmacokinetics and could explain variability in efficacy and adverse drug reactions associated with antiretroviral drugs. Notions related to the major enzymes (CYP450s and UGTs) involved in antiretroviral metabolism and drugtransporters are reviewed with an attention paid on genetic polymorphisms. Genetic polymorphisms affecting the activity or the expression of membrane proteins in the transport of drugs would be highlighted with examples such as neurotoxicity with efavirenz, nephrotoxicity with tenofovir, hepatotoxicity with nevirapine and hyperlibirubinemia associated with indinavir and atazanavir. The objective is to provide a better understanding on mechanisms involved in drugdisposition of antiretroviral helping out health care providers in the management of pharmacotherapy of HIV-infected patients.