Use of ARV Drug Levels in DBS to Assess and Manage ART Adherence in South Africa

 描述(由申请人提供)：针对RFA-AI-14-071，我们建议确定干血斑(DBS)中替诺福韦-二磷酸(TFV-DP)检测的实用性，作为南非抗逆转录病毒治疗(ART)依从性的客观衡量标准。对这种活性抗逆转录病毒药物(ARV)合成代谢产物的测量可量化药物摄入量，可提供病毒血症的早期预警，并可用于向患者和提供者提供激励和可操作的反馈。激励坚持的反馈具有额外的重要性，因为更多的患者在感觉健康的时候更早开始抗逆转录病毒治疗，因此可能难以维持长期坚持。常规(通常是每年一次)病毒载量测定往往错过了预防病毒血症和/或产生抗药性病毒的机会。客观依从性措施可以为早期干预提供及时的反馈，但现有措施在有效性、患者/提供者负担、费用和可接受性等方面存在问题。没有任何迹象表明是否真的摄入了一剂。联合调查员安德森开发了一种在DBS中检测TFV-DP的方法，它反映了过去几周/几个月的药物摄入情况；可能导致这种检测方法在护理点应用的研究正在开发中。尽管该检测的特点是成人感染艾滋病毒，但我们提议的项目将检验其在撒哈拉以南非洲的现实世界环境中用于治疗而不是预防的效用。这项研究将提供关键信息，如果没有这些信息，此类技术的有效推广将受到严重影响--特别是在资源匮乏的情况下，如南非。在我们最近的试点研究之后(Rhemen等人)在SA的HIV+患者中使用安德森的DBS TFV-DP试验，我们建议通过两个特定的目标来研究在这种低资源环境下使用这种试验来评估和管理ART的依从性。目的1：在250名接受抗逆转录病毒治疗的成年人中，我们将通过使用每月药物合成代谢和VL分析以及连续12个月以上的威西平输出，来确定该方法是否能够提供客观的、临床相关的和可操作的依从性衡量标准，这些患者接受了为期12个月的≥治疗。我们将比较DBS TFV-DP试验和Wisepill预测病毒血症的能力；确定DBS TFV-DP-在实际应用中预测病毒血症的下降幅度和下降时间；并记录仍处于病毒抑制状态的患者的DBS TFV-DP水平范围。目标2：我们将制定每月向患者和提供者提供化验反馈的信息和程序，并在一项小型试点研究(N=60)中，检查提供者和患者在收到此信息后的行为。研究结果将向该领域提供信息，并为未来的更大规模试验提供试点数据，以建立这种反馈对患者依从性相关行为和提供者医疗管理的影响。这项拟议的研究代表了美国和南非的行为科学家、药理学家和临床医生之间正在进行的、创新的和富有成效的多学科合作伙伴关系。

 DESCRIPTION (provided by applicant): In response to RFA-AI-14-071, we propose to determine the utility of assay of tenofovir-diphosphate (TFV-DP) in dried blood spots (DBS) as an objective measure of adherence to antiretroviral treatment (ART) in South Africa. Measurement of this active antiretroviral medication (ARV) anabolite quantifies medication ingestion, may provide early warning of viremia, and may be used to provide motivating and actionable feedback to patients and providers. Feedback that motivates adherence has additional importance as more patients begin ART earlier in their disease course when they are feeling healthy and, as a result, may have problems sustaining long-term adherence. Routine (often only annual) viral load measurement often misses the opportunity to prevent viremia and/or development of resistant virus. Objective adherence measures could provide timely feedback for earlier intervention, however, existing measures have problems with validity; patient/provider burden; and expense and acceptability. None indicates if a dose is actually ingested. Co-Investigator, Anderson, developed an assay of TFV-DP in DBS that reflects drug ingestion over past weeks/months; research likely to lead to a point- of-care application of this assay is under development. Although the assay has been characterized in HIV- adults, our proposed project would examine its utility for treatment rather than prevention in real-world settings in Sub Saharan Africa. This research will provide critical information without which the effective roll-out of such technologies would be significantly compromised - especially in low-resource settings, such as South Africa. Following our recent pilot study (Remien et al.) using Anderson's DBS TFV-DP assay among HIV+ patients in SA, we propose research on the use of this assay to assess and manage ART adherence in this low-resource setting through two Specific Aims. Aim 1: Among 250 HIV+ adults on ART containing TFV for ≥12 months, we will determine the ability of this assay to provide an objective, clinically relevant, and actionable measure of adherence by using monthly drug anabolite and VL assays along with continuous Wisepill output over 12 months. We will compare the abilities of the DBS TFV-DP assay and Wisepill to predict viremia; determine the magnitude of decrease in DBS TFV-DP - in real-world use - that predicts viremia and by how long; and document the range of DBS TFV-DP levels in patients who remain virally suppressed. Aim 2: We will develop messages and procedures for giving patients and providers monthly feedback from the assay and, in a small pilot study (N=60), examine provider and patient behaviors in response to receiving this information. Findings will inform the field and provide pilot data for a future larger trial to establish the imact of such feedback on patients' adherence-related behaviors and on medical management by providers. The proposed research represents an ongoing, innovative, and productive multidisciplinary partnership among behavioral scientists, pharmacologists, and clinicians in the US and South Africa.