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

使用 DBS 中的抗逆转录病毒药物水平来评估和管理南非的 ART 依从性

• 批准号: 9191334
• 负责人: Catherine Orrell
• 金额: $ 107.78万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-15 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9191334
• 关键词: Address; Adherence; Adult; Africa South of the Sahara; Anti-Retroviral Agents; Behavior; Behavioral; Biological Assay; Blood; Clinical; Country; Data; Development; Devices; Diphosphates; Disease; Dose; Early Intervention; Early treatment; Epidemic; Erythrocytes; Failure; Feedback; Feeling; Future; HIV; Health; Hematologic Agents; Hour; Individual; Ingestion; Laboratories; Lead; Measurement; Measures; Medical; Medication Management; Methods; Monitor; Outcome; Output; Patient Self-Report; Patients; Pharmaceutical Preparations; Pharmacy facility; Pilot Projects; Prevention; Procedures; Prospective Studies; Provider; Public Health; Research; Research Personnel; Resistance development; Resources; Sampling; Scientist; Signal Transduction; South Africa; South African; Spottings; Technology; Tenofovir; Time; Viral; Viral Load result; Viral load measurement; Viremia; Work; clinical care; clinically relevant; compliance behavior; improved; innovation; medication compliance; monitoring device; multidisciplinary; nucleoside analog; pharmacokinetic characteristic; pill; point of care; pre-exposure prophylaxis; prevent; public health relevance; response; sample collection; treatment adherence; viral rebound; virus development

 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.

 描述（由申请人提供）：针对 RFA-AI-14-071，我们建议确定干血斑 (DBS) 中替诺福韦二磷酸盐 (TFV-DP) 测定的效用，作为南非抗逆转录病毒治疗 (ART) 依从性的客观衡量标准。这种活性抗逆转录病毒药物 (ARV) 合成代谢物的测量可量化药物摄入量，可以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性和可操作的反馈。激励依从性的反馈具有额外的重要性，因为越来越多的患者在病程早期、感觉健康时开始接受 ART，因此可能在维持长期依从性方面存在问题。 常规（通常仅每年一次）病毒载量测量常常错过预防病毒血症和/或耐药病毒发展的机会。客观的依从性措施可以为早期干预提供及时反馈，但现有措施存在有效性问题；患者/提供者的负担；以及费用和可接受性。没有一个表明剂量是否被实际摄入。联合研究员 Anderson 开发了一种 DBS 中 TFV-DP 的检测方法，可反映过去几周/几个月的药物摄入情况；可能导致该测定法在现场护理应用的研究正在开发中。尽管该检测已在成人艾滋病毒中进行了表征，但我们提出的项目将检查其在撒哈拉以南非洲的现实环境中治疗而非预防的效用。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，特别是在南非等资源匮乏的地区。 继我们最近（Remien 等人）在南澳州 HIV+ 患者中使用 Anderson 的 DBS TFV-DP 检测进行试点研究之后，我们建议研究使用该检测方法通过两个具体目标来评估和管理这种资源匮乏环境中的 ART 依从性。目标 1：在 250 名接受含有 TFV 的 ART 治疗≥12 个月的 HIV+ 成人中，我们将通过每月使用药物合成代谢物和 VL 测定以及 12 个月内的连续 Wisepill 输出来确定该测定提供客观、临床相关且可操作的依从性测量的能力。我们将比较 DBS TFV-DP 检测和 Wisepill 预测病毒血症的能力；确定 DBS TFV-DP 在实际使用中的下降幅度，以预测病毒血症以及持续多久；并记录病毒仍处于抑制状态的患者的 DBS TFV-DP 水平范围。目标 2：我们将开发信息和程序，以便每月向患者和提供者提供检测反馈，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。研究结果将为该领域提供信息，并为未来更大规模的试验提供试点数据，以确定此类反馈对患者依从性相关行为和提供者医疗管理的影响。拟议的研究代表了美国和南非行为科学家、药理学家和临床医生之间持续、创新和富有成效的多学科合作伙伴关系。