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Influence of UGT1A1 and SLC22A6 polymorphisms on the population pharmacokinetics and pharmacodynamics of raltegravir in HIV-infected adults: a NEAT001/ANRS143 sub-study

dc.rights.licenseopenen_US
dc.contributor.authorGURJAR, Rohan
dc.contributor.authorDICKINSON, Laura
dc.contributor.authorCARR, Daniel
dc.contributor.authorSTOHR, Wolfgang
dc.contributor.authorBONORA, Stefano
dc.contributor.authorOWEN, Andrew
dc.contributor.authorD'AVOLIO, Antonio
dc.contributor.authorCURSLEY, Adam
dc.contributor.authorDE CASTRO, Nathalie
dc.contributor.authorFATKENHEUER, Gerd
dc.contributor.authorVANDEKERCKHOVE, Linos
dc.contributor.authorDI PERRI, Giovanni
dc.contributor.authorPOZNIAK, Anton
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorSCHWIMMER, Christine
dc.contributor.authorRAFFI, Francois
dc.contributor.authorBOFFITO, Marta
dc.date.accessioned2022-12-07T08:37:04Z
dc.date.available2022-12-07T08:37:04Z
dc.date.issued2022-10-20
dc.identifier.issn1473-1150 (Electronic) 1470-269X (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/170488
dc.description.abstractEnUsing concentration-time data from the NEAT001/ARNS143 study (single sample at week 4 and 24), we determined raltegravir pharmacokinetic parameters using nonlinear mixed effects modelling (NONMEM v.7.3; 602 samples from 349 patients) and investigated the influence of demographics and SNPs (SLC22A6 and UGT1A1) on raltegravir pharmacokinetics and pharmacodynamics. Demographics and SNPs did not influence raltegravir pharmacokinetics and no significant pharmacokinetic/pharmacodynamic relationships were observed. At week 96, UGT1A1*28/*28 was associated with lower virological failure (p = 0.012), even after adjusting for baseline CD4 count (p = 0.048), but not when adjusted for baseline HIV-1 viral load (p = 0.082) or both (p = 0.089). This is the first study to our knowledge to assess the influence of SNPs on raltegravir pharmacodynamics. The lack of a pharmacokinetic/pharmacodynamic relationship is potentially an artefact of raltegravir's characteristic high inter and intra-patient variability and also suggesting single time point sampling schedules are inadequate to thoroughly assess the influence of SNPs on raltegravir pharmacokinetics.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enClinical pharmacology
dc.subject.enPharmacogenetics
dc.subject.enPharmacokinetics
dc.title.enInfluence of UGT1A1 and SLC22A6 polymorphisms on the population pharmacokinetics and pharmacodynamics of raltegravir in HIV-infected adults: a NEAT001/ANRS143 sub-study
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41397-022-00293-5en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed36266537en_US
bordeaux.journalPharmacogenomics Journalen_US
bordeaux.page1-7en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamAHEAD_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03887832
hal.version1
hal.date.transferred2022-12-07T08:37:18Z
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Pharmacogenomics%20Journal&rft.date=2022-10-20&rft.spage=1-7&rft.epage=1-7&rft.eissn=1473-1150%20(Electronic)%201470-269X%20(Linking)&rft.issn=1473-1150%20(Electronic)%201470-269X%20(Linking)&rft.au=GURJAR,%20Rohan&DICKINSON,%20Laura&CARR,%20Daniel&STOHR,%20Wolfgang&BONORA,%20Stefano&rft.genre=article


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