PrEP and ART adherence monitoring using dried blood spots

使用干血斑监测 PrEP 和 ART 依从性

• 批准号: 8652949
• 负责人: PETER L. ANDERSON
• 金额: $ 65.57万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-15 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8652949
• 关键词: Adherence; Adolescent Medicine Trials Network; Antiviral Agents; Blood; Caring; Characteristics; Chemoprophylaxis; Clinical; Collection; Data; Development; Diabetes Mellitus; Diagnosis; Diphosphates; Directly Observed Therapy; Disadvantaged; Dose; Drug Exposure; Drug Formulations; Drug resistance; Electronics; Erythrocytes; Exhibits; Failure; Fingers; Future; Generic Drugs; Glucose; Glycosylated Hemoglobin; Goals; HIV; HIV Seropositivity; Hair; Half-Life; Health; Hemoglobin; Holidays; Human; Individual; Intervention; Kinetics; Location; Measurement; Measures; Methods; Modeling; Monitor; Outcome; Participant; Patient Self-Report; Patients; Pattern; Persons; Pharmaceutical Preparations; Pharmacy facility; Plasma; Process; Prodrugs; Public Health; RNA; Randomized; Records; Regimen; Resources; Safety; Site; Spottings; Tenofovir; Tenofovir disoproxil fumarate; Testing; Therapeutic; Time; Translating; Validation; Venipunctures; Viremia; Visit; antiretroviral therapy; base; cohort; data modeling; design; efavirenz; emtricitabine; improved; monitoring device; novel; open label; pill; prospective; public health relevance; therapy adherence; volunteer

DESCRIPTION (provided by applicant): Inadequate adherence to HIV pre-exposure chemoprophylaxis (PrEP) and antiretroviral therapy (ART) is common, and the leading cause of therapeutic failure. Despite this damaging impact on human health, reliable, convenient methods with which to quantify adherence routinely are not available. This application proposes a new quantitative approach to routinely monitor adherence to tenofovir disoproxil fumarate (TDF)-based PrEP and ART. TDF-based regimens are the cornerstone of PrEP and ART with approximately 80% of ART patients and 100% of PrEP patients receiving TDF-based therapy. We discovered that tenofovir-diphosphate (TFV-DP), the active form of TFV, has a 17 day half-life in red blood cells (RBC) with low variability. These characteristics are analogous to glycosylated hemoglobin A1C, which is measured as standard- of-care to quantitatively monitor cumulative glucose exposure for diabetes. We propose that the level of TFV-DP in RBC can be used in a similar way to quantitatively monitor cumulative drug exposure (adherence) for TDF-based PrEP and ART. We showed that the level of TFV-DP in RBC can be quantified using dried blood spots (DBS), which offers significant advantages such as low expense and easy collection and processing requirements. The proposed study will determine the effect of adherence rate on the level of TFV-DP in DBS. Forty eight HIV-negative volunteers will be randomized to 33%, 67% and 100% of daily dosing with TDF-FTC. All dosing will be directly observed therapy (DOT). A randomized incomplete block design with a washout period will be employed such that participants receive 2 of 3 dosing regimens for 12 weeks each. A separate cohort of 32 HIV-positive volunteers will receive daily DOT with TDF-FTC-based therapy. Expected levels of TFV-DP in DBS in the setting of DOT will be defined, compared in HIV-positive versus negative persons, and used to construct a model that predicts adherence quantitatively for PrEP and ART. We will immediately translate our findings to interpret TFV-DP in DBS that are currently being collected for several pivotal PrEP demonstration projects where adherence monitoring is a key outcome. We believe that TFV-DP in DBS, as a new quantitative measure of adherence, has the potential to make an immediate and lasting public health impact.

描述（由申请人提供）：遵守HIV侵蚀前化学预防（PREP）和抗逆转录病毒疗法（ART）的不足是常见的，并且是治疗衰竭的主要原因。尽管对人类健康的损害影响，但通常无法使用可靠，方便的方法来量化依从性。该应用程序提出了一种新的定量方法，以常规监测对基于替诺福韦的富马酸（TDF）的准备和艺术的依从性。基于TDF的方案是PREP和ART的基石，大约80％的ART患者和100％接受基于TDF治疗的Prep患者。我们发现Tenofovir-Diphosphate（TFV-DP）（TFV-DP）是TFV的活性形式，在红细胞（RBC）中具有17天的半衰期，其可变性较低。这些特征类似于糖基化的血红蛋白A1C，该特征以标准的标准测量，以定量监测糖尿病的累积葡萄糖暴露。我们建议，RBC中的TFV-DP水平可用于基于TDF的PREP和ART的定量监测累积药物暴露（依从性）。我们表明，可以使用干血点（DBS）来量化RBC中TFV-DP的水平，该水位具有显着优势，例如低费用以及易于收集和处理要求。拟议的研究将确定粘附率对DBS中TFV-DP水平的影响。 TDF-FTC的每日剂量的48名HIV阴性志愿者将被随机分为33％，67％和100％。所有给药将直接观察到治疗（DOT）。将采用一个随机不完整的块设计，以使参与者在3个剂量方案中有2个剂量，每人12周。单独组成的32个HIV阳性志愿者将接受基于TDF-FTC的治疗的每日点。将定义DB中DBS中TFV-DP的预期水平，以HIV阳性与负面的人进行比较，并用于构建一个模型，该模型可以定量地预测依从性，以定量地依从性。我们将立即转化我们的发现，以解释DBS中的TFV-DP，目前正在为几个关键的预备演示项目收集，这些项目依从性监测是关键结果。我们认为，DBS中的TFV-DP作为依从性的新定量量度，有可能立即产生公共卫生的影响。