title: Antiretroviral drug toxicity in  relation to pharmacokinetics,  metabolic profile and  pharmacogenetics.
abstract: BACKGROUND
  Besides therapeutic effectiveness, drug tolerability is a key issue for treatments that must be taken indefinitely. Given the high prevalence of toxicity in HIV therapy, the factors implicated in drug-induced morbidities should be identified in order to improve the safety, tolerability and adherence to the treatments. Current approaches have focused almost exclusively on parent drug concentrations; whereas recent evidence suggests that drug metabolites resulting from complex genetic and environmental influences can also contribute to treatment outcome. Pharmacogenetic variations have shown to play a relevant role in the variability observed in antiretroviral drug exposure, clinical response and sometimes toxicity. The integration of pharmacokinetic, pharmacogenetic and metabolic determinants will more probably address current therapeutic needs in patients.
  
  
  METHODS
  This review offers a concise description of three classes of antiretroviral drugs. The review looks at the metabolic profile of these drugs and gives a comprehensive summary of the existing literature on the influence of pharmacogenetics on their pharmacokinetics and metabolic pathways, and the associated drug or metabolite toxicity.
  
  
  CONCLUSIONS
  Due to the high prevalence of toxicity and the related risk of low adherence to the treatments, association of kinetic, genetic and metabolic markers predictive of therapeutic or toxicity outcomes could represent a more complete approach for optimizing antiretroviral therapy.
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital and University of Lausanne, Beaumont, Lausanne, Switzerland.
authors.forename: Mona
authors.initials: M
authors.lastname: Arab-Alameddine
authors.forename: Laurent Arhtur
authors.initials: LA
authors.lastname: Décosterd
authors.forename: Thierry
authors.initials: T
authors.lastname: Buclin
authors.forename: Amalio
authors.initials: A
authors.lastname: Telenti
authors.forename: Chantal
authors.initials: C
authors.lastname: Csajka
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology; D004053:Diethylpropion; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D010597:Pharmacogenetics
chemical_list: D019380:Anti-HIV Agents; D004053:Diethylpropion