Pharmacokinetics-based adherence measures for antiretroviral therapy in HIV-infected Kenyan children.
Pharmacokinetics-based adherence measures for antiretroviral therapy in HIV-infected Kenyan children.
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DOI：
10.7448/ias.20.1.21157
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发表时间：
2017-06-15
影响因子：
6
通讯作者：
Vreeman RC
中科院分区：
文献类型：
--
作者：
Tu W;Nyandiko WM;Liu H;Slaven JE;Scanlon ML;Ayaya SO;Vreeman RC
背景：传统的药物依从性测量不考虑药物的药代动力学（PK）特性，可能歪曲真实的治疗暴露。方法：在接受包括奈韦拉平（NVP）在内的抗逆转录病毒治疗的艾滋病毒感染的肯尼亚儿童群体中，我们使用了一个单室模型，该模型具有先前建立的PK参数和药物事件监测系统（MEMS®）记录的给药时间，以估计个体患者在1个月的随访期间的平均血浆NVP （Cp）浓度。在完全遵循的给药方案和频率下计算预期NVP浓度（Cp '）。两者之间的比值（R = Cp/Cp’）表征了患者与预期水平相比的NVP暴露。R值越小，粘附性越差。我们通过评估其与MEMS®定义的依从性、CD4%和1个月时抽查NVP血浆浓度的关系来验证R。结果：在152名儿童（82名女性）的数据中，儿童的平均年龄为7.7岁（范围为1.5-14.9），NVP的平均年龄为2.2岁。平均MEMS®依从性为79%。R均值为1.11 （SD 0.37）。R与MEMS®依从性呈正相关（p < 0.0001），低于中位数的R值与较低的NVP药物浓度（p = 0.0018）和较低的CD4% （p = 0.0178）显著相关，证实R值越小表明依从性越差。结论：提出了依从性措施，R，捕获患者服药行为和PK性质。
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.