Tu, WanzhuNyandiko, Winstone M.Liu, HaiSlaven, James E.Scanlon, Michael L.Ayaya, Samuel O.Vreeman, Rachel C.2018-05-152018-05-152017-06-15Tu, W., Nyandiko, W. M., Liu, H., Slaven, J. E., Scanlon, M. L., Ayaya, S. O., & Vreeman, R. C. (2017). Pharmacokinetics-based adherence measures for antiretroviral therapy in HIV-infected Kenyan children. Journal of the International AIDS Society, 20(1), 21157. http://doi.org/10.7448/IAS.20.1.21157https://hdl.handle.net/1805/16181BACKGROUND: 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.en-USAttribution 3.0 United StatesNevirapineAdherenceElectronic dose monitoringMeasurement validationPediatricsPharmacokineticsArticle