title: Impact of pharmacogenetics on CNS side effects related to efavirenz.
abstract: OBJECTIVE
  This article evaluates which genetic factors are involved in CNS toxicity related to long-term treatment with efavirenz (EFV) standard doses and their relationship with plasma concentrations.
  
  
  METHODS
  A total of 119 HIV-positive patients, in which 1350 EFV plasma concentrations, 68 SNPs and 14 EFV-related adverse effects (AEs) were analyzed.
  
  
  RESULTS
  Overall, 32.77% of patients reported CNS toxicity and 8.40% had concentrations above the therapeutic range. A correlation was mainly found between patients with global CNS AEs and high EFV maximum steady-state plasma concentration (p = 1.47 × 10(-6)). A preliminary analysis confirmed that CYP2B6*6 (516G>T and 785A>G) was the most highly correlated (p = 0.005) with AEs and high plasma concentrations. In a second analysis adjusting for maximum steady-state plasma concentration, suggestive genetic associations were found between BCRP 421C>A, MRP1 816G>A, 5-HT2A 102C>T and different AEs.
  
  
  CONCLUSIONS
  The finding of the involvement of these SNPs in EFV toxicity opens the door for further studies to confirm their validity and for their application in the future clinical practice. Original submitted 18 February 2013; Revision submitted 17 May 2013.
authors.affiliation: Pharmacy Service, University Hospital of Salamanca, Salamanca, Spain.
authors.forename: Almudena
authors.initials: A
authors.lastname: Sánchez Martín
authors.forename: Salvador
authors.initials: S
authors.lastname: Cabrera Figueroa
authors.forename: Raquel
authors.initials: R
authors.lastname: Cruz Guerrero
authors.forename: Liliana Porras
authors.initials: LP
authors.lastname: Hurtado
authors.forename: Alfonso Dominguez-Gil
authors.initials: AD
authors.lastname: Hurlé
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo Álvarez
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D054316:Biomarkers, Pharmacological; D002493:Central Nervous System Diseases / Q000139:chemically induced / Q000235:genetics*; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6; D005260:Female; D006678:HIV / Q000472:pathogenicity; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D054316:Biomarkers, Pharmacological; D003521:Cyclopropanes; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; C098320:efavirenz