Novel Mass Spectrometry Imaging Methods to Quantify Antiretroviral Adherence

量化抗逆转录病毒依从性的新型质谱成像方法

基本信息

  • 批准号:
    10260722
  • 负责人:
  • 金额:
    $ 74.96万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-01-01 至 2022-12-31
  • 项目状态:
    已结题

项目摘要

Adherence to antiretroviral (ARV) therapy is critical for achieving HIV RNA suppression in HIV- infected patients and for preventing HIV acquisition in uninfected individuals using pre-exposure prophylaxis (PrEP). Yet a high level of adherence is challenging for HIV-infected individuals on life-long ARVs, and for HIVnegative individuals using daily PrEP who are not at daily risk for HIV acquisition. Poor adherence was primarily responsible for a lack of drug effectiveness in multiple recent double-blind, placebo-controlled PrEP studies. These studies found that counting product returns and using patient self-report significantly over predicted adherence as measured by ARV concentrations in blood plasma or cells. Since the consequences of poor or intermittent adherence are significant, valid measures of adherence are critical for optimizing the effectiveness of both HIV treatment and prevention, in both the clinic and research settings. Blood plasma or intracellular concentration monitoring have been considered the “gold standard” for determining if an ARV has been ingested, and is a common marker for therapeutic drug monitoring or clinical trial adherence monitoring. However, this approach has its own set of limitations, including being invasive, requiring advanced processing or storage (e.g. intracellular measures), being a short-term measure of drug taking behavior (depending on the half-life of the analyte), and requiring long turn-around times or substantial sample processing prior to analysis. We propose the use of infra-red (IR) matrix-assisted laser desorption electrospray ionization (MALDESI) technology for mass spectrometry imaging (MSI) to visualize and quantify ARV concentrations in hair. Our hypothesis is that IR-MALDESI MSI can rapidly quantify ARV concentrations, provide evidence of drug ingestion non-invasively and longitudinally, and allow for clinician/researcher and patient/study participant feedback on adherence performance. Three specific aims are proposed: 1) Develop IR-MALDESI MSI hair protocols for high sensitivity and accuracy to quantify 11 ARVs in 5 therapeutic drug classes, 2) Conduct 3 structured dose proportionality studies to develop mathematical benchmarks for real- time IR-MALDESI hair adherence monitoring in both PrEP and HIV treatment applications, and validate the benchmarks with a Phase 2 PrEP study, and 3) In the setting of REAL TIME clinical monitoring, investigate the acceptability, appropriateness, and feasibility of using hair IRMALDESI MSI to provide HIV+ patients with feedback regarding longitudinal patterns of medication adherence. The goal of this work is to develop a simple, noninvasive, longitudinal depiction of ARV adherence that will provide high clarity feedback for both clinicians and patients. RELEVANCE (See instructions): It is important to identify if someone is taking a medication regularly and as prescribed to optimize their health and wellbeing, but sometimes patients have trouble remembering if and when they miss doses; other times, even though patients are taking their medication, it is not getting into the body in the right amount. Quickly monitoring medications in 5-10 hair strands using our novel imaging technology called IR-MALDESI will allow patients and their doctors to see how much medication they are exposed to over 1 or more months, and help identify challenges to taking medication in both research and clinical settings. This proposal will optimize and explore the acceptability and feasibility of using IR-MALDESI for monitoring medications in hair.
坚持抗逆转录病毒(ARV)治疗对于实现HIV感染者的HIV RNA抑制至关重要 并使用暴露前预防措施(PrEP)防止非感染者感染艾滋病毒。 然而,对于终身服用抗逆转录病毒药物的艾滋病毒感染者来说,高水平的坚持是具有挑战性的, HIV阴性的人,每天使用PrEP,他们没有每天感染艾滋病毒的风险。依从性差是 对近期多个双盲、安慰剂对照的PrEP缺乏药物有效性负有主要责任 学习。这些研究发现,计算产品退货和使用患者自我报告显著超过 通过血浆或细胞中的ARV浓度衡量,预测依从性。因为后果是 较差或间歇性的依从性是重要的,有效的依从性措施对于优化 在临床和研究环境中,艾滋病毒治疗和预防的有效性。血浆或 细胞内浓度监测一直被认为是确定ARV是否 已被摄取,是治疗药物监测或临床试验依从性的常见标志 监控。然而,这种方法有它自己的一组限制,包括侵入性、需要 高级处理或存储(例如,细胞内测量),是吸毒的短期测量 行为(取决于分析物的半衰期),并且需要较长的周转时间或 分析前的样品处理。我们建议使用红外线(IR)基质辅助激光解吸 电喷雾电离(Maldesi)技术用于质谱成像(MSI)的可视化和定量 头发中的抗逆转录病毒浓度。我们的假设是,IR-Maldesi MSI可以快速定量ARV浓度, 提供非侵入性和纵向药物摄入的证据,并允许临床医生/研究人员和 患者/研究参与者对依从性表现的反馈。提出了三个具体目标:1)发展 IR-Maldesi MSI毛发方案用于5种治疗药物中11种抗逆转录病毒药物的高灵敏度和准确性 课程,2)进行3项结构化剂量比例研究,以开发实际- 在PrEP和HIV治疗应用中进行时间IR-Maldesi头发粘连监测,并验证 基准与第二阶段PrEP研究,以及3)在实时临床监测的环境中,调查 使用Hair IRMALDESI MSI为HIV+患者提供 关于药物依从性的纵向模式的反馈。这项工作的目标是开发一种 对ARV依从性的简单、非侵入性的纵向描述,将为两者提供高清晰的反馈 临床医生和患者。 相关性(请参阅说明): 确定某人是否定期并按照处方服药以优化其健康是很重要的 和幸福感,但有时患者很难记住他们是否以及何时错过了剂量;其他时候, 即使患者正在服用药物,它也没有以正确的量进入体内。速战速决 使用我们名为IR-Maldesi的新型成像技术监测5-10根头发中的药物将允许 患者和他们的医生了解他们在1个月或更长时间内接触了多少药物,并提供帮助 确定在研究和临床环境中服用药物的挑战。这项建议将优化和 探讨IR-Maldesi用于头发药物监测的可接受性和可行性。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Development and validation of an LC-MS/MS assay for the quantification of dolutegravir extracted from human hair.
开发和验证 LC-MS/MS 测定法,用于定量从人发中提取的多替拉韦。
  • DOI:
    10.1007/s00216-018-1394-y
  • 发表时间:
    2018
  • 期刊:
  • 影响因子:
    4.3
  • 作者:
    Sykes,Craig;Blake,Kimberly;White,Nicole;Schauer,AmandaP;Guzman,BryanB;Cottrell,MackenzieL;Tamraz,Bani;Kashuba,AngelaDM
  • 通讯作者:
    Kashuba,AngelaDM
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Angela D Kashuba其他文献

Angela D Kashuba的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Angela D Kashuba', 18)}}的其他基金

Novel Mass Spectrometry Imaging Methods to Quantify Antiretroviral Adherence
量化抗逆转录病毒依从性的新型质谱成像方法
  • 批准号:
    9040663
  • 财政年份:
    2016
  • 资助金额:
    $ 74.96万
  • 项目类别:
Multi-Species Mechanisms of Drug Bio-distribution in HIV Tissue Reservoirs
HIV组织储库中药物生物分布的多物种机制
  • 批准号:
    9226028
  • 财政年份:
    2014
  • 资助金额:
    $ 74.96万
  • 项目类别:
Multi-Species Mechanisms of Drug Bio-distribution in HIV Tissue Reservoirs
HIV组织储库中药物生物分布的多物种机制
  • 批准号:
    9003024
  • 财政年份:
    2014
  • 资助金额:
    $ 74.96万
  • 项目类别:
Multi-Species Mechanisms of Drug Bio-distribution in HIV Tissue Reservoirs
HIV组织储库中药物生物分布的多物种机制
  • 批准号:
    8706563
  • 财政年份:
    2014
  • 资助金额:
    $ 74.96万
  • 项目类别:
Clinical Pharmacology & Analytical Chemistry Core
临床药理学
  • 批准号:
    8531837
  • 财政年份:
    2013
  • 资助金额:
    $ 74.96万
  • 项目类别:
Preventing HIV Infection in Women: Targeting Antiretrovirals to Mucosal Tissues
预防女性艾滋病毒感染:针对粘膜组织的抗逆转录病毒药物
  • 批准号:
    8493986
  • 财政年份:
    2011
  • 资助金额:
    $ 74.96万
  • 项目类别:
Clinical Pharmacology & Analytical Chemistry Core
临床药理学
  • 批准号:
    8329990
  • 财政年份:
    2011
  • 资助金额:
    $ 74.96万
  • 项目类别:
Preventing HIV Infection in Women: Targeting Antiretrovirals to Mucosal Tissues
预防女性艾滋病毒感染:针对粘膜组织的抗逆转录病毒药物
  • 批准号:
    8284294
  • 财政年份:
    2011
  • 资助金额:
    $ 74.96万
  • 项目类别:
UPLC-MS/MS to Support Preclinical and Clinical Antiretroviral Pharmacology Studie
UPLC-MS/MS 支持临床前和临床抗逆转录病毒药理学研究
  • 批准号:
    8051351
  • 财政年份:
    2011
  • 资助金额:
    $ 74.96万
  • 项目类别:
Pharmacology Core
药理学核心
  • 批准号:
    8326902
  • 财政年份:
    2011
  • 资助金额:
    $ 74.96万
  • 项目类别:

相似海外基金

RESISTANCE OF HIV-1 TO ANTI-RETROVIRAL AGENTS
HIV-1 对抗逆转录病毒药物的耐药性
  • 批准号:
    3030975
  • 财政年份:
    1993
  • 资助金额:
    $ 74.96万
  • 项目类别:
POLYMERICS DELIVERY SYSTEMS FOR ANTI-RETROVIRAL AGENTS
抗逆转录病毒药物的聚合物递送系统
  • 批准号:
    3489187
  • 财政年份:
    1990
  • 资助金额:
    $ 74.96万
  • 项目类别:
DEVELOPMENTAL VIROLOGY RESEARCH--RESISTANCE TO ANTI-RETROVIRAL AGENTS
发育病毒学研究——抗逆转录病毒药物的耐药性
  • 批准号:
    2335293
  • 财政年份:
  • 资助金额:
    $ 74.96万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了