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

TitleEffects of age on antiretroviral plasma drug concentration in HIV-infected subjects undergoing routine therapeutic drug monitoring.
Publication TypeJournal Article
Year of Publication2013
AuthorsWinston A, Jose S, Gibbons S, Back D, Stöhr W, Post F, Fisher M, Gazzard B, Nelson M, Gilson R, Orkin C, Johnson M, Palfreeman A, Chadwick D, Leen C, Schwenk A, Anderson J, Gompels M, Dunn D, Khoo S and Sabin C
Corporate AuthorsUK Collaborative HIV Cohort Study
JournalJ Antimicrob Chemother
Volume68
Issue6
Pagination1354-9
Date Published2013 Jun
ISSN1460-2091
KeywordsAdult, Aged, Aging, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Chromatography, High Pressure Liquid, Cohort Studies, Drug Monitoring, Female, Hepatitis C, HIV Infections, Humans, Liver Function Tests, Male, Mass Spectrometry, Middle Aged, Reverse Transcriptase Inhibitors, United Kingdom, Viral Load
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.

DOI10.1093/jac/dkt029
Alternate JournalJ. Antimicrob. Chemother.
PubMed ID23435690
Grant ListG0901364 / / Medical Research Council / United Kingdom
G0000199 / / Medical Research Council / United Kingdom
G0600337 / / Medical Research Council / United Kingdom
G0900274 / / Medical Research Council / United Kingdom