Gurjar, Rohan, Dickinson, Laura 
ORCID: 0000-0001-5557-9396, Carr, Daniel, Stohr, Wolfgang, Bonora, Stefano, Owen, Andrew ORCID: 0000-0002-9819-7651, D'Avolio, Antonio, Cursley, Adam, De Castro, Nathalie, Fatkenheuer, Gerd et al (show 6 more authors)
(2022)
Influence of <i>UGT1A1</i> and <i>SLC22A6</i> polymorphisms on the population pharmacokinetics and pharmacodynamics of raltegravir in HIV-infected adults: a NEAT001/ANRS143 sub-study.
PHARMACOGENOMICS JOURNAL, 23 (1).
pp. 14-20.
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NEAT001/ANRS143 Study Group, Humans, HIV Infections, Anti-HIV Agents, Viral Load, Polymorphism, Genetic, Adult, Raltegravir Potassium |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 03 Nov 2022 10:34 |
| Last Modified: | 17 Oct 2023 19:11 |
| DOI: | 10.1038/s41397-022-00293-5 |
| Open Access URL: | https://doi.org/10.1038/s41397-022-00293-5 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3165968 |
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