Pharmacokinetics-based adherence measures for antiretroviral therapy in HIV-infected Kenyan children
dc.contributor.author | Tu, Wanzhu | |
dc.contributor.author | Nyandiko, Winstone M. | |
dc.contributor.author | Liu, Hai | |
dc.contributor.author | Slaven, James E. | |
dc.contributor.author | Scanlon, Michael L. | |
dc.contributor.author | Ayaya, Samuel O. | |
dc.contributor.author | Vreeman, Rachel C. | |
dc.contributor.department | Biostatistics, School of Public Health | en_US |
dc.date.accessioned | 2018-05-15T14:11:37Z | |
dc.date.available | 2018-05-15T14:11:37Z | |
dc.date.issued | 2017-06-15 | |
dc.description.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. | en_US |
dc.eprint.version | Final published version | en_US |
dc.identifier.citation | Tu, 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.20.1.21157 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/16181 | |
dc.language.iso | en_US | en_US |
dc.publisher | Wiley | en_US |
dc.relation.isversionof | 10.7448/IAS.20.1.21157 | en_US |
dc.relation.journal | Journal of the International AIDS Society | en_US |
dc.rights | Attribution 3.0 United States | |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | |
dc.source | PMC | en_US |
dc.subject | Nevirapine | en_US |
dc.subject | Adherence | en_US |
dc.subject | Electronic dose monitoring | en_US |
dc.subject | Measurement validation | en_US |
dc.subject | Pediatrics | en_US |
dc.subject | Pharmacokinetics | en_US |
dc.title | Pharmacokinetics-based adherence measures for antiretroviral therapy in HIV-infected Kenyan children | en_US |
dc.type | Article | en_US |