比较药丸计数和患者自我报告与 DBS 替诺福韦浓度作为 ART 依从性测量，以评估津巴布韦哈拉雷失败的青少年和年轻成年人队列的病毒学结果和 HIV 耐药性。
Comparing pill counts and patient self-reports versus DBS tenofovir concentrations as ART adherence measurements with virologic outcomes and HIV drug resistance in a cohort of adolescents and young adults failing ART in Harare, Zimbabwe.
机构信息
Internal Medicine Unit, Department of Primary Healthcare Sciences, University of Zimbabwe, Harare, Zimbabwe.
Translational Pharmacology Research Core, State University of New York at Buffalo, NY14203, USA.
出版信息
J Infect Public Health. 2024 Sep;17(9):102500. doi: 10.1016/j.jiph.2024.102500. Epub 2024 Jul 17.
BACKGROUND
Monitoring adherence presents a challenge in adolescents and it is prudent to explore several options for determining their level of adherence. This study sought to determine ART adherence levels in adolescents and young adults (on a tenofovir-containing regimen) failing ART as measured by self-reports, pill counts and DBS tenofovir concentrations and to compare levels of agreement among the methods and determine the ability of each method to predict virological suppression.
METHODS
This was a cohort study involving 107 adolescents and young adults between 10 and 24 years failing ART with viral load > 400copies/ml at enrolment. Pill count (PC) records, self-reports (SR) and DBS tenofovir concentrations (done by liquid Chromatography with tandem mass spectrometry (LC-MS/MS)) were used to determine adherence in adolescent participants failing ART in Harare. The latter was used as the reference method with a cut-off of 64 ng/ml. Determination of DBS tenofovir concentrations was also performed to rule out inadequate viral response due to low cumulative drug exposure despite high adherence (≥90 %). Longitudinal analysis was performed to determine the correlation of viral loads (VL) with adherence. The Kappa (k) coefficient was used to evaluate the level of agreement among the 3 methods.
RESULTS
Poor level of agreement was found between PC records and DBS tenofovir concentrations (k = -0.115). Moderate agreement was found between DBS and SR methods (k = 0.0557). Slight agreement was found between PC and SR methods (k = 0.0078). Adherence was dependent on age at HIV diagnosis (p = 0.0184) and ART initiation (p = 0.0265). Participants who were adherent were six times more likely to be suppressed at end point than their non-adherent counterparts (OR=5.7 CI 2.1 - 16.5, p < 0.0001).
CONCLUSIONS
Self-reported measure of adherence and pill counts exhibited poor agreement with the reference method used i.e. DBS tenofovir concentrations and are thus not effective methods of predicting virological suppression.
TRIAL IDENTIFICATION
Participants in the present study were a subset of those in the PESU intervention ClinicalTrials.gov Identifier: NCT02833441.
背景
监测青少年的依从性是一项挑战，因此探索确定其依从性水平的多种选择是明智之举。本研究旨在确定接受基于替诺福韦的方案治疗但治疗失败的青少年和年轻成人（ART）的 ART 依从性水平，方法是通过自我报告、药物计数和 DBS 替诺福韦浓度进行测量，并比较这些方法之间的一致性水平，确定每种方法预测病毒学抑制的能力。
方法
这是一项队列研究，纳入了在入组时病毒载量>400 拷贝/ml 的 107 名接受 ART 治疗失败的 10 至 24 岁青少年和年轻成人。通过液体色谱-串联质谱法（LC-MS/MS）测定的药物计数（PC）记录、自我报告（SR）和 DBS 替诺福韦浓度用于确定在哈拉雷接受 ART 治疗失败的青少年参与者的依从性，后者被用作参考方法，截断值为 64ng/ml。还进行了 DBS 替诺福韦浓度测定，以排除尽管依从性高（≥90%）但由于累积药物暴露量低导致病毒学反应不足的情况。进行了纵向分析以确定病毒载量（VL）与依从性的相关性。Kappa（k）系数用于评估 3 种方法之间的一致性水平。
结果
PC 记录与 DBS 替诺福韦浓度之间发现较差的一致性（k=-0.115）。DBS 与 SR 方法之间存在中度一致性（k=0.0557）。PC 与 SR 方法之间存在轻度一致性（k=0.0078）。依从性取决于 HIV 诊断时的年龄（p=0.0184）和 ART 开始时间（p=0.0265）。依从性高的参与者在终点时被抑制的可能性是其不依从性的六倍（OR=5.7 CI 2.1-16.5，p<0.0001）。
结论
自我报告的依从性测量和药物计数与我们使用的参考方法（即 DBS 替诺福韦浓度）显示出较差的一致性，因此不是预测病毒学抑制的有效方法。
试验识别码
本研究的参与者是 PESU 干预临床试验的一部分（ClinicalTrials.gov 标识符：NCT02833441）。
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