Antiviral pharmacology and adherence in drug users

抗病毒药理学和吸毒者的依从性

• 批准号: 9274955
• 负责人: JENNIFER JUSTICE KISER
• 金额: $ 52.16万
• 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/9274955
• 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; Human; Impairment; Individual; Ingestion; Knowledge; Life; Link; Liver Failure; Measures; Monitor; Oral; Participant; Patient Self-Report; Patients; Pattern; Pharmaceutical Preparations; Pharmacology; Pharmacy facility; Plasma; Population; Randomized; Regimen; Research; Resistance; Savings; Services; Signal Transduction; Technology; Testing; Time; Underrepresented Populations; Viral hepatitis; Virus; Visual; Wireless Technology; Work; base; co-infection; forgiveness; medication compliance; neglect; novel; patient population; pill; portability; predictive marker; prospective; public health relevance; 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）： 所有患有丙型肝炎病毒（HCV）的美国人中，大约有一半是吸毒者，但他们接受HCV治疗的可能性最低。吸毒者是非遵守者的，因此拒绝了潜在的挽救生命的疗法。只能通过该人群中的前瞻性药物和依从性研究来确认或消除这一假设。通过本应用中提出的工作的客观，定量衡量依从性的定量测量将大大增强此类研究，将使用直接作用抗病毒剂（DAA）治疗60种HIV/HCV共同感染的吸毒者，并随机地接收直接观察到的DAA治疗（DOT）（dot）与无直接观察的治疗（NO-DOT）。随机分配到无点的患者将无线观察到的治疗（WOT），涉及使用便携式药物分配器，该分配器将信号发送给服务器的日期和时间时，分配器打开时。在AIM 1中，将在随机分配到DOT与NO-DOT的那些DAA浓度中进行比较。 DAA药物目不会的刺激学还将定义为临床因素，例如肝损伤程度以及伴随休闲和抗逆转录病毒药物的使用。目的是量化该人群中的依从性以及可变依从性对药物浓度的影响。在AIM 2中，DAA浓度（血浆，细胞，头发）将与使用WOT和DOT鉴定的依从性模式有关。目的是确定预测该人群依从性的药物浓度生物标志物。在AIM 3中，将建立DAA依从性（通过WOT和DOT和药物浓度衡量）与治愈率之间的关系。目的是定义HCV治疗所需的依从性程度。该项目对人类健康很重要，因为它将治疗被忽视的患者人群，使用技术来使依从性监测方便，评估，基于药代动力学的依从性措施，确定遵守性对HCV治疗可能性的贡献，并在DAA“宽恕”上产生第一个数据。提出的工作将产生急需的药理学和客观依从性数据，以鼓励吸毒者对HCV的治疗。