title: Pharmacogenetics of toxicity, plasma trough concentration and treatment outcome with nevirapine-containing regimen in anti-retroviral-naïve HIV-infected adults: an exploratory study of the TRIANON ANRS 081 trial.
abstract: The aim of this exploratory study was to investigate in a homogeneous population of anti-retroviral naïve HIV-1-infected adults, the relationships between genetic polymorphisms involved in nevirapine metabolism [CYP2B6 516G>T, 785A>G and 1459C>T; CYP3A5 6986A>G (CYP3A5*3)], transport (ABCB1 2677G>T/A and 3435C>T), and antigen recognition (HLA-DRB1*0101), and the hepatic and/or cutaneous toxicity occurring within the first 8 or 72 weeks of treatment, plasma trough concentrations (C(trough) ) at week 8 and immuno-virological response to nevirapine at week 24. Associations between genetic polymorphisms and toxicity, C(trough) and response to nevirapine were performed in a population of 72 HIV-1 positive and nevirapine-treated patients followed during 72 weeks, as part of the previous study called: ANRS081 'Trianon' trial. Among the 18 patients who developed toxicity events during the 72 weeks of the study, 12 patients exhibited early toxicity before week 8. No significant association could be evidenced between any of the analysed single nucleotide polymorphisms (SNPs) and nevirapine early or global toxicity, pharmacokinetics and immuno-virological responses even though a possible association between CYP2B6 516G>T and 1459C>T and the trough level of nevirapine was suggested.
authors.affiliation: Department of Molecular Genetics, Pharmacogenetics and Hormonology, Assistance Publique-Hôpitaux de Paris, Bicêtre Hospital, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Gozalo
authors.forename: Laurence
authors.initials: L
authors.lastname: Gérard
authors.forename: Pascale
authors.initials: P
authors.lastname: Loiseau
authors.forename: Laurence
authors.initials: L
authors.lastname: Morand-Joubert
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.forename: Pierre
authors.initials: P
authors.lastname: Dellamonica
authors.forename: Laurent
authors.initials: L
authors.lastname: Becquemont
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Aboulker
authors.forename: Odile
authors.initials: O
authors.lastname: Launay
authors.forename: Céline
authors.initials: C
authors.lastname: Verstuyft
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood / Q000627:therapeutic use / Q000633:toxicity; D023241:Antiretroviral Therapy, Highly Active; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D018791:CD4 Lymphocyte Count; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000821:virology; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D019829:Nevirapine / Q000097:blood / Q000627:therapeutic use / Q000633:toxicity; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019380:Anti-HIV Agents; D059811:HLA-DRB1 Chains; C487961:HLA-DRB1*01:01 antigen; D019829:Nevirapine; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; C510164:CYP3A5 protein, human; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating