eprintid: 10158094 rev_number: 24 eprint_status: archive userid: 699 dir: disk0/10/15/80/94 datestamp: 2022-10-27 14:57:11 lastmod: 2022-10-27 14:57:11 status_changed: 2022-10-27 14:57:11 type: article metadata_visibility: show sword_depositor: 699 creators_name: Gurjar, Rohan creators_name: Dickinson, Laura creators_name: Carr, Daniel creators_name: Stöhr, Wolfgang creators_name: Bonora, Stefano creators_name: Owen, Andrew creators_name: D'Avolio, Antonio creators_name: Cursley, Adam creators_name: De Castro, Nathalie creators_name: Fätkenheuer, Gerd creators_name: Vandekerckhove, Linos creators_name: Di Perri, Giovanni creators_name: Pozniak, Anton creators_name: Schwimmer, Christine creators_name: Raffi, François creators_name: Boffito, Marta creators_name: NEAT001/ANRS143 Study Group, title: Influence of UGT1A1 and SLC22A6 polymorphisms on the population pharmacokinetics and pharmacodynamics of raltegravir in HIV-infected adults: a NEAT001/ANRS143 sub-study ispublished: inpress divisions: UCL divisions: J38 divisions: D65 divisions: B02 keywords: Clinical pharmacology, Pharmacogenetics, Pharmacokinetics note: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. abstract: Using 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. date: 2022-10-20 date_type: published publisher: Springer Science and Business Media LLC official_url: https://doi.org/10.1038/s41397-022-00293-5 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1984492 doi: 10.1038/s41397-022-00293-5 medium: Print-Electronic pii: 10.1038/s41397-022-00293-5 lyricists_name: Stohr, Wolfgang lyricists_id: WSTOH63 actors_name: Stohr, Wolfgang actors_id: WSTOH63 actors_role: owner full_text_status: public publication: The Pharmacogenomics Journal event_location: United States issn: 1470-269X citation: Gurjar, Rohan; Dickinson, Laura; Carr, Daniel; Stöhr, Wolfgang; Bonora, Stefano; Owen, Andrew; D'Avolio, Antonio; ... NEAT001/ANRS143 Study Group; + view all <#> Gurjar, Rohan; Dickinson, Laura; Carr, Daniel; Stöhr, Wolfgang; Bonora, Stefano; Owen, Andrew; D'Avolio, Antonio; Cursley, Adam; De Castro, Nathalie; Fätkenheuer, Gerd; Vandekerckhove, Linos; Di Perri, Giovanni; Pozniak, Anton; Schwimmer, Christine; Raffi, François; Boffito, Marta; NEAT001/ANRS143 Study Group; - view fewer <#> (2022) Influence of UGT1A1 and SLC22A6 polymorphisms on the population pharmacokinetics and pharmacodynamics of raltegravir in HIV-infected adults: a NEAT001/ANRS143 sub-study. The Pharmacogenomics Journal 10.1038/s41397-022-00293-5 <https://doi.org/10.1038/s41397-022-00293-5>. (In press). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10158094/7/Stohr_s41397-022-00293-5.pdf