Effects of age on antiretroviral plasma drug concentration in HIV-infected subjects undergoing routine therapeutic drug monitoring

Winston, Alan, Jose, Sophie, Gibbons, Sara, Back, David, Stohr, Wolfgang, Post, Frank, Fisher, Martin and The UK Collaborative HIV Cohort Study, (2013) Effects of age on antiretroviral plasma drug concentration in HIV-infected subjects undergoing routine therapeutic drug monitoring. Journal of Antimicrobial Chemotherapy, 68 (6). pp. 1354-1359. ISSN 0305-7453

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Abstract

OBJECTIVES

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.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Brighton and Sussex Medical School
Subjects: R Medicine > RC Internal medicine > RC0109 Infectious and parasitic diseases
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Depositing User: Ellen Thomas
Date Deposited: 19 Aug 2013 10:18
Last Modified: 19 Aug 2013 10:18
URI: http://srodev.sussex.ac.uk/id/eprint/45864
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