Antiviral pharmacology and adherence in drug users

抗病毒药理学和吸毒者的依从性

• 批准号: 9105779
• 负责人: JENNIFER JUSTICE KISER
• 金额: $ 52.18万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-15 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9105779
• 关键词: AIDS prevention; Accounting; Address; Adherence; Affect; American; Anti-Retroviral Agents; Antiviral Agents; Biological Markers; Cessation of life; Cirrhosis; Clinical; Clinical Trials; Data; Directly Observed Therapy; Disease; Dose; Drug Interactions; Drug Kinetics; Drug usage; Drug user; Goals; HIV; HIV/HCV; Hair; Health; Hepatic; Hepatitis C; Hepatitis C co-infection; Hepatitis C virus; Human; Impairment; Individual; Ingestion; Knowledge; Life; Link; Liver Failure; Measures; Monitor; Oral; Participant; Patient Self-Report; Patients; Pattern; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Pharmacy facility; Plasma; Population; Randomized; Regimen; Research; Resistance; Services; Signal Transduction; Technology; Testing; Time; Underrepresented Populations; Viral hepatitis; Visual; Work; base; forgiveness; medication compliance; neglect; novel; patient population; pill; prospective; response; tool

 DESCRIPTION (provided by applicant): Approximately one half of all Americans living with Hepatitis C virus (HCV) are drug users, yet they are the least likely to receive HCV treatment. Drug users are presumed non-adherent and therefore denied potentially life-saving therapy. This assumption can only be confirmed or dispelled through prospective pharmacologic and adherence studies in this population. Such studies would be greatly enhanced by an objective, quantitative measure of adherence which does not currently exist in the HCV field. Through the work proposed in this application, sixty HIV/HCV co-infected drug users will be treated with direct acting antiviral agents (DAA) and randomized to receive directly observed DAA therapy (DOT) vs. no directly observed therapy (no-DOT). Patients randomized to no-DOT will have wirelessly observed therapy (WOT) which involves use of a portable medication dispenser that sends a signal to a server with the date and time when the dispenser is opened. In Aim 1, DAA concentrations will be compared in those randomized to DOT vs. no-DOT. DAA pharmacokinetics will also be defined accounting for clinical factors like degree of hepatic impairment and use of concomitant recreational and antiretroviral drugs. The goal is to quantify adherence in this population and the effect of variable adherence on drug concentrations. In Aim 2, DAA concentrations (plasma, cellular, hair) will be linked with adherence patterns identified using WOT and DOT. The goal is to identify a drug concentration biomarker that predicts adherence in this population. In Aim 3, the relationship between DAA adherence (as measured by WOT and DOT and drug concentrations) and rate of cure will be established. The goal is to define the degree of adherence needed for HCV cure. This project is important to human health as it will treat a neglected patient population, use technology to make adherence monitoring convenient, evaluate novel, pharmacokinetic-based adherence measures, determine the contribution of adherence to the likelihood of HCV cure, and generate the first data on DAA "forgiveness". The work proposed will generate much needed pharmacology and objective adherence data to encourage the treatment of HCV in drug users.

 描述（由申请人提供）： 大约一半的丙型肝炎病毒 (HCV) 感染美国人是吸毒者，但他们接受丙型肝炎病毒治疗的可能性最小。吸毒者被认为不依从，因此无法接受可能挽救生命的治疗。这一假设只能通过针对该人群的前瞻性药理学和依从性研究来证实或消除。通过客观、定量的依从性测量，此类研究将得到极大的加强，而目前 HCV 领域尚不存在这种测量。通过本申请中提出的工作，60 名同时感染 HIV/HCV 的吸毒者将接受直接作用抗病毒药物 (DAA) 治疗，并随机接受直接观察的 DAA 治疗 (DOT) 与不接受直接观察的治疗 (no-DOT)。随机接受 no-DOT 的患者将接受无线观察治疗 (WOT)，其中涉及使用便携式药物分配器，该分配器向服务器发送信号，其中包含分配器打开的日期和时间。在目标 1 中，将比较随机使用 DOT 与无 DOT 的 DAA 浓度。 DAA 药代动力学也将根据临床因素进行定义，例如肝损伤程度以及同时使用娱乐药物和抗逆转录病毒药物。目标是量化该人群的依从性以及不同依从性对药物浓度的影响。在目标 2 中，DAA 浓度（血浆、细胞、头发）将与使用 WOT 和 DOT 识别的粘附模式相关联。目标是确定预测该人群依从性的药物浓度生物标志物。在目标 3 中，将建立 DAA 依从性（通过 WOT 和 DOT 以及药物浓度测量）与治愈率之间的关系。目标是确定 HCV 治愈所需的依从程度。该项目对人类健康非常重要，因为它将治疗被忽视的患者群体，利用技术使依从性监测变得方便，评估新颖的、基于药代动力学的依从性措施，确定依从性对 HCV 治愈可能性的贡献，并生成有关 DAA“宽恕”的第一个数据。拟议的工作将产生急需的药理学和客观依从性数据，以鼓励吸毒者进行丙型肝炎治疗。