AI Article Synopsis
- The study analyzed raltegravir pharmacokinetics using data from the NEAT001/ARNS143 study involving 349 patients at weeks 4 and 24, utilizing a complex statistical modeling approach.
- It found that demographics and specific genetic variants (SNPs) did not significantly affect raltegravir pharmacokinetics or pharmacodynamics, indicating a lack of clear relationships between these factors.
- However, a genetic variant (UGT1A1*28/*28) was linked to a reduced risk of virological failure at week 96, though this association was influenced by other baseline variables like HIV-1 viral load.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9584256 | PMC |
| http://dx.doi.org/10.1038/s41397-022-00293-5 | DOI Listing |
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