A novel REverSe Transcriptase Chain Termination (RESTRICT) assay for near-patient, objective monitoring of long-term PrEP adherence

一种新型 REverSe 转录酶链终止 (RESTRICT) 测定，可用于患者附近长期 PrEP 依从性的客观监测

• 批准号: 10513809
• 负责人: Paul K Drain
• 金额: $ 77.14万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-11-09 至 2025-10-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10513809
• 关键词: Address; Adherence; Adult; Algorithmic Analysis; Biological Assay; Blood specimen; Calibration; Client; Clinic; Clinical; Counseling; Data; Data Analyses; Data Collection; Diabetes Mellitus; Diphosphates; Drug Kinetics; Fumarates; Glycosylated hemoglobin A; Goals; Guidelines; HIV; Half-Life; Human; Ingestion; Interview; Laboratories; Liquid Chromatography; Measurement; Measures; Medical center; Monitor; Oral; Outpatients; Patient Self-Report; Patients; Pharmaceutical Preparations; Population; Predisposition; Preparation; Procedures; Provider; Qualifying; RNA-Directed DNA Polymerase; Randomized; Reporting; Research; Resources; Sampling; Structure; Supportive care; Surveys; Tenofovir; Testing; Training; Universities; Urine; Validation; Visit; Washington; Whole Blood; acceptability and feasibility; cellular targeting; clinical efficacy; clinically relevant; emtricitabine; experience; follow-up; implementation science; implementation study; improved; in-vitro diagnostics; medication compliance; meetings; novel; novel strategies; pill; pre-exposure prophylaxis; prevent; prospective; tandem mass spectrometry; tool; transmission process; validation studies

ABSTRACT Oral pre-exposure prophylaxis (PrEP), composed of tenofovir disoproxil fumarate and emtricitabine, is effective for preventing HIV acquisition, but PrEP efficacy is highly dependent on drug adherence. In several trials and implementation studies, PrEP clients have difficulties maintaining adequate adherence and persistence, and monitoring their PrEP use is challenging. PrEP providers have relied on self-reported adherence, which is often inaccurate and unreliable. The lack of an objective PrEP adherence monitoring tool has led to inefficient counseling and poor supportive care. To address these issues, we completed a randomized pharmacokinetic study to determine drug levels during controlled directly-observed PrEP. Longer-term metabolites, such as tenofovir-diphosphate (TFV-DP) (~17-day half-life), provide a more accurate picture of long-term PrEP adherence. We recently developed a novel enzymatic assay that semi-quantitatively measures the concentration of TFV-DP by measuring inhibition of reverse transcriptase, which is the cellular target of oral PrEP drugs. In this proposal, our primary objectives are optimizing the REverSe TRanscrIptase Chain Termination (RESTRICT) assay to measure drug concentrations of PrEP clients, to establish validation for CLIA criteria when implemented in a near-patient clinical lab, and to evaluate the feasibility and acceptability of using the RESTRICT assay for drug level measurement among PrEP clients and providers. We will test our central hypotheses with three specific aims: (1) to calibrate and optimize the RESTRICT assay for measuring long-term TFV-DP drug concentrations, compared to gold-standard liquid chromatography tandem mass spectrometry (LC-MS/MS) measurement; (2) to validate the RESTRICT assay for meeting established CLIA criteria to enable clinical reporting of an objective near-patient measure for monitoring long-term TFV-DP drug concentrations; (3) to evaluate the feasibility and acceptability of near-patient TFV-DP testing among PrEP clients and providers at a major PrEP clinic in Seattle. Our proposed study will be the first to validate a rapid, near-patient long-term objective measure of oral PrEP adherence. This study will also provide crucial data on the feasibility and acceptability of a novel approach for improving PrEP delivery and monitoring to prevent HIV transmission. The results of this study will develop a new tool that may help improve PrEP delivery in the US and worldwide.

摘要