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Effects of age on antiretroviral plasma drug concentration in HIV-infected subjects undergoing routine therapeutic drug monitoring
journal contribution
posted on 2023-06-08, 15:29 authored by Alan Winston, Sophie Jose, Sara Gibbons, David Back, Wolfgang Stohr, Frank Post, Martin Fisher, The UK Collaborative HIV Cohort StudyOBJECTIVES The pharmacokinetic and pharmacodynamic effects of antiretroviral therapy may differ in older compared with younger subjects with HIV infection. We aimed to assess factors associated with plasma antiretroviral drug exposure, including age, within a large HIV-infected cohort undergoing therapeutic drug monitoring (TDM). METHODS Data from the Liverpool TDM Registry were linked with the UK Collaborative HIV Cohort (CHIC) Study. All TDM of protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) was included and in order to account for different antiretroviral drugs the plasma concentrations were standardized by group measurements according to drug, dosing and timing of TDM. Regression modelling was used to evaluate associations of drug exposure with age and clinical parameters, including hepatic transaminase results and time to antiretroviral treatment modification. RESULTS Data from 3589 TDM samples were available from 2447 subjects. The greatest numbers of plasma concentrations were assessed for lopinavir (22.4%), efavirenz (18.5%), atazanavir (17.0%) and saquinavir (11.6%). As age increased, median standardized NNRTI concentrations remained constant, whereas PI concentrations increased (correlation coefficient 0.04, P?=?0.033). In a regression analysis stratified by antiretroviral drug class, standardized plasma concentrations were significantly associated with age for PIs (0.05 increase in standard deviation of drug concentration with each 10 year increase in age, P?=?0.044), but not for NNRTIs or other clinical parameters, including hepatic transaminase results or time to antiretroviral treatment modification. CONCLUSIONS With increasing age, statistically significant rises in plasma PI exposure, but not NNRTI exposure, were observed. The clinical relevance of this observation merits further investigation.
History
Publication status
- Published
Journal
Journal of Antimicrobial ChemotherapyISSN
0305-7453Publisher
Oxford University PressExternal DOI
Issue
6Volume
68Page range
1354-1359Department affiliated with
- BSMS Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2013-08-19Usage metrics
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