title: Effects of age on antiretroviral plasma drug concentration in HIV-infected subjects undergoing routine therapeutic drug monitoring.
abstract: OBJECTIVE
  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.
authors: Section of Infectious Diseases, Division of Medicine, Imperial College London, St Mary's Hospital Campus, Norfolk Place, London W2 1PG, UK. a.winston@imperial.ac.uk
authors: Alan
authors: A
authors: Winston
authors: Sophie
authors: S
authors: Jose
authors: Sara
authors: S
authors: Gibbons
authors: David
authors: D
authors: Back
authors: Wolfgang
authors: W
authors: Stohr
authors: Frank
authors: F
authors: Post
authors: Martin
authors: M
authors: Fisher
authors: Brian
authors: B
authors: Gazzard
authors: Mark
authors: M
authors: Nelson
authors: Richard
authors: R
authors: Gilson
authors: Chloe
authors: C
authors: Orkin
authors: Margaret
authors: M
authors: Johnson
authors: Adrian
authors: A
authors: Palfreeman
authors: David
authors: D
authors: Chadwick
authors: Clifford
authors: C
authors: Leen
authors: Achim
authors: A
authors: Schwenk
authors: Jane
authors: J
authors: Anderson
authors: Mark
authors: M
authors: Gompels
authors: David
authors: D
authors: Dunn
authors: Saye
authors: S
authors: Khoo
authors: Caroline
authors: C
authors: Sabin
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000097:blood / Q000493:pharmacokinetics; D006113:United Kingdom; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors
keywords: TDM; ageing; antiretroviral therapy; cohort; pharmacokinetics