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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
Author(s) -
Gozalo Claire,
Gérard Laurence,
Loiseau Pascale,
MorandJoubert Laurence,
Peytavin Gilles,
Molina JeanMichel,
Dellamonica Pierre,
Becquemont Laurent,
Aboulker JeanPierre,
Launay Odile,
Verstuyft Céline
Publication year - 2011
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2011.00780.x
Subject(s) - nevirapine , medicine , cyp2b6 , pharmacology , pharmacogenetics , population , toxicity , regimen , immunology , genotype , viral load , biology , human immunodeficiency virus (hiv) , antiretroviral therapy , genetics , environmental health , cytochrome p450 , metabolism , cyp3a4 , gene
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.