Pharmacokinetics-based adherence measures for antiretroviral therapy in HIV-infected Kenyan children

Wanzhu Tu, Winstone M. Nyandiko, Hai Liu, James E. Slaven, Michael L. Scanlon, Samuel O. Ayaya, Rachel Vreeman

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

BACKGROUND: Traditional medication adherence measures do not account for the pharmacokinetic (PK) properties of the drugs, potentially misrepresenting true therapeutic exposure.

METHODS: In a population of HIV-infected Kenyan children on antiretroviral therapy including nevirapine (NVP), we used a one-compartment model with previously established PK parameters and Medication Event Monitoring Systems (MEMS®)-recorded dosing times to estimate the mean plasma concentration of NVP (Cp) in individual patients during 1 month of follow-up. Intended NVP concentration (Cp') was calculated under a perfectly followed dosing regimen and frequency. The ratio between the two (R = Cp/Cp') characterized the patient's NVP exposure as compared to intended level. Smaller R values indicated poorer adherence. We validated R by evaluating its association with MEMS®-defined adherence, CD4%, and spot-check NVP plasma concentrations assessed at 1 month.

RESULTS: In data from 152 children (82 female), children were mean age 7.7 years (range 1.5-14.9) and on NVP an average of 2.2 years. Mean MEMS® adherence was 79%. The mean value of R was 1.11 (SD 0.37). R was positively associated with MEMS® adherence (p < 0.0001), and lower-than-median R values were significantly associated with lower NVP drug concentrations (p = 0.0018) and lower CD4% (p = 0.0178), confirming a smaller R value showed poorer adherence.

CONCLUSION: The proposed adherence measures, R, captured patient drug-taking behaviours and PK properties.

Original languageEnglish (US)
Number of pages1
JournalJournal of the International AIDS Society
Volume20
Issue number1
DOIs
StatePublished - Jun 15 2017

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Nevirapine
Pharmacokinetics
HIV
Therapeutics
Pharmaceutical Preparations
Medication Adherence

Keywords

  • adherence
  • electronic dose monitoring
  • measurement validation
  • Nevirapine
  • pediatrics
  • pharmacokinetics

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Pharmacokinetics-based adherence measures for antiretroviral therapy in HIV-infected Kenyan children. / Tu, Wanzhu; Nyandiko, Winstone M.; Liu, Hai; Slaven, James E.; Scanlon, Michael L.; Ayaya, Samuel O.; Vreeman, Rachel.

In: Journal of the International AIDS Society, Vol. 20, No. 1, 15.06.2017.

Research output: Contribution to journalArticle

Tu, Wanzhu ; Nyandiko, Winstone M. ; Liu, Hai ; Slaven, James E. ; Scanlon, Michael L. ; Ayaya, Samuel O. ; Vreeman, Rachel. / Pharmacokinetics-based adherence measures for antiretroviral therapy in HIV-infected Kenyan children. In: Journal of the International AIDS Society. 2017 ; Vol. 20, No. 1.
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abstract = "BACKGROUND: Traditional medication adherence measures do not account for the pharmacokinetic (PK) properties of the drugs, potentially misrepresenting true therapeutic exposure.METHODS: In a population of HIV-infected Kenyan children on antiretroviral therapy including nevirapine (NVP), we used a one-compartment model with previously established PK parameters and Medication Event Monitoring Systems (MEMS{\circledR})-recorded dosing times to estimate the mean plasma concentration of NVP (Cp) in individual patients during 1 month of follow-up. Intended NVP concentration (Cp') was calculated under a perfectly followed dosing regimen and frequency. The ratio between the two (R = Cp/Cp') characterized the patient's NVP exposure as compared to intended level. Smaller R values indicated poorer adherence. We validated R by evaluating its association with MEMS{\circledR}-defined adherence, CD4{\%}, and spot-check NVP plasma concentrations assessed at 1 month.RESULTS: In data from 152 children (82 female), children were mean age 7.7 years (range 1.5-14.9) and on NVP an average of 2.2 years. Mean MEMS{\circledR} adherence was 79{\%}. The mean value of R was 1.11 (SD 0.37). R was positively associated with MEMS{\circledR} adherence (p < 0.0001), and lower-than-median R values were significantly associated with lower NVP drug concentrations (p = 0.0018) and lower CD4{\%} (p = 0.0178), confirming a smaller R value showed poorer adherence.CONCLUSION: The proposed adherence measures, R, captured patient drug-taking behaviours and PK properties.",
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