Investigating Multiple PK and PD Relationships for TB-HIV (IMPPRove TB-HIV)

调查 TB-HIV 的多重 PK 和 PD 关系 (IMPPRove TB-HIV)

基本信息

  • 批准号:
    10882249
  • 负责人:
  • 金额:
    $ 81.73万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-08-21 至 2024-07-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Tuberculosis (TB) is the leading infectious cause of mortality globally after COVID-19. TB and HIV interact synergistically, each worsening the outcomes of the other. A key driver of unfavorable TB treatment outcomes is suboptimal drug exposures. However, target drug concentrations of first-line TB drugs and cumulative exposure thresholds needed for optimal clinical outcomes, post-TB lung health, and prevention of emergence of resistance are not defined, particularly in programmatic settings. In our study entitled “Investigating Multiple PK and PD Relationships for TB-HIV (IMPPRove TB-HIV)," we will leverage the Tuberculosis Sentinel Research Network (TB SRN), a large global platform cohort study for coordinated observational TB research conducted among persons with pulmonary TB with and without HIV, within the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium in six IeDEA regions, to conduct pharmacokinetic-pharmacodynamic (PK-PD) analyses, using a nested case-cohort design. We will measure individual PK via collection of dried blood spots (DBS), which are easy to collect, store, and ship, and cumulative drug exposure in hair, which reflects both adherence and PK. In Aim 1 (PK-PD aim), we will examine the impact of TB drug PK and cumulative drug exposure on risk of unfavorable TB treatment outcomes (death, failure, recurrence) among individuals with pulmonary TB, with or without HIV. In Aim 2 (PK-resistance aim), we will investigate the impact of drug exposures on emergence of TB drug resistance mutations. In Aim 3 (PK-lung health aim), we will evaluate the association between anti-TB drug exposures and post-TB lung disease and longitudinal lung health. Thus, the IMPPRove study aims to elucidate the relationships between drug exposures and unfavorable TB treatment outcomes, poor lung health, and resistance under field conditions, in a large multinational patient population, taking into account HIV status and other factors known to affect these outcomes. The goal is to inform optimization of TB treatment (right dose, right patient) to improve clinically-important outcomes for patients.
项目概要 结核病 (TB) 是继 COVID-19 之后全球范围内导致死亡的主要传染病。结核病和艾滋病毒相互作用 协同作用,每一个都会使另一个的结果恶化。结核病治疗不利的关键驱动因素 结果是次优的药物暴露。然而,一线结核病药物的目标药物浓度和 最佳临床结果、结核病后肺部健康和预防结核病所需的累积暴露阈值 阻力的出现没有被定义,特别是在程序设置中。在我们的研究中题为 “调查 TB-HIV 的多重 PK 和 PD 关系 (IMPPRove TB-HIV)”,我们将利用 结核病前哨研究网络 (TB SRN),一个大型全球平台队列研究,旨在协调 在感染和未感染艾滋病毒的肺结核患者中进行的观察性结核病研究 国际流行病学数据库评估艾滋病 (IeDEA) 联盟在六个 IeDEA 地区开展 使用嵌套病例队列设计进行药代动力学-药效(PK-PD)分析。我们将测量 通过收集干血斑 (DBS) 进行个体 PK,干血斑易于收集、储存和运输,并且 头发中的累积药物暴露,反映了依从性和 PK。在目标 1(PK-PD 目标)中,我们将 检查结核病药物 PK 和累积药物暴露对不利结核病治疗风险的影响 患有或不患有艾滋病毒的肺结核患者的结局(死亡、失败、复发)。目标 2 (PK耐药目标),我们将研究药物暴露对结核病耐药性出现的影响 突变。在目标 3(PK-肺部健康目标)中,我们将评估抗结核药物暴露之间的关联 以及结核病后肺部疾病和纵向肺部健康。因此,IMPPRove 研究旨在阐明 药物暴露与不良结核病治疗结果、肺部健康状况不佳和 考虑到艾滋病毒状况,在现场条件下,在大量跨国患者群体中进行耐药性 以及已知影响这些结果的其他因素。目标是为结核病治疗的优化提供信息(右 剂量,正确的患者)以改善患者的临床重要结果。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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

{{ 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 }}

Kelly E. Dooley其他文献

Development and validation of a time-varying correction factor for QT interval assessment in drug-resistant tuberculosis patients
耐药结核病患者 QT 间期评估的时变校正因子的开发与验证
  • DOI:
    10.1016/j.ijantimicag.2025.107460
  • 发表时间:
    2025-04-01
  • 期刊:
  • 影响因子:
    4.600
  • 作者:
    Thanakorn Vongjarudech;Anne-Gaëlle Dosne;Bart Remmerie;Kelly E. Dooley;James C.M. Brust;Gary Maartens;Graeme Meintjes;Mats O. Karlsson;Elin M. Svensson
  • 通讯作者:
    Elin M. Svensson
Development and validation of a liquid chromatography-tandem mass spectrometry assay for the simultaneous analysis of isoniazid and pyrazinamide in cerebrospinal fluid
  • DOI:
    10.1016/j.jpba.2024.116613
  • 发表时间:
    2025-03-15
  • 期刊:
  • 影响因子:
  • 作者:
    Sydwell Poulo Maputla;Anton Joubert;Sandra Castel;Marthinus van der Merwe;Edda Zangenberg;Sean Wasserman;Kelly E. Dooley;Lubbe Wiesner
  • 通讯作者:
    Lubbe Wiesner
Risk-stratified treatment for drug-susceptible pulmonary tuberculosis
药物敏感型肺结核的风险分层治疗
  • DOI:
    10.1038/s41467-024-53273-7
  • 发表时间:
    2024-10-30
  • 期刊:
  • 影响因子:
    15.700
  • 作者:
    Vincent K. Chang;Marjorie Z. Imperial;Patrick P. J. Phillips;Gustavo E. Velásquez;Payam Nahid;Andrew Vernon;Ekaterina V. Kurbatova;Susan Swindells;Richard E. Chaisson;Susan E. Dorman;John L. Johnson;Marc Weiner;Amina Jindani;Thomas Harrison;Erin E. Sizemore;William Whitworth;Wendy Carr;Kia E. Bryant;Deron Burton;Kelly E. Dooley;Melissa Engle;Pheona Nsubuga;Andreas H. Diacon;Nguyen Viet Nhung;Rodney Dawson;Radojka M. Savic
  • 通讯作者:
    Radojka M. Savic
SEGURANÇA E EFICÁCIA DA TERAPIA ANTIRRETROVIRAL BASEADA EM DOLUTEGRAVIR, NA SEMANA 48, EM ADULTOS COINFECTADOS HIV/TB
  • DOI:
    10.1016/j.bjid.2018.10.027
  • 发表时间:
    2018-12-01
  • 期刊:
  • 影响因子:
  • 作者:
    Kelly E. Dooley;Richard Kaplan;Noluthando Mwelase;Beatriz Grinsztejn;Eduardo Ticona;Marcus Lacerda;Omar Sued;Elena Belonosova;Mounir Ait‐Khaled;Kostas Angelis;Dannae Brown;Rajendra Singh;Christine Talarico;Allan Tenorio;Michael Keegan;Michael Aboud;Roberto Zajdenverg
  • 通讯作者:
    Roberto Zajdenverg
Tuberculosis Preventive Treatment in High TB-Burden Settings: A State-of-the-Art Review
  • DOI:
    10.1007/s40265-024-02131-3
  • 发表时间:
    2024-12-28
  • 期刊:
  • 影响因子:
    14.400
  • 作者:
    Violet Chihota;Makaita Gombe;Amita Gupta;Nicole Salazar-Austin;Tess Ryckman;Christopher J. Hoffmann;Sylvia LaCourse;Jyoti S. Mathad;Vidya Mave;Kelly E. Dooley;Richard E. Chaisson;Gavin Churchyard
  • 通讯作者:
    Gavin Churchyard

Kelly E. Dooley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('Kelly E. Dooley', 18)}}的其他基金

Pharmacology and Pharmacometrics Core
药理学和药理学核心
  • 批准号:
    10431024
  • 财政年份:
    2022
  • 资助金额:
    $ 81.73万
  • 项目类别:
Second Generation InSTIs for the Treatment of HIV-1 in patients with TB co-infection on Rifampicin-based Treatment in KwaZulu Natal, South Africa
在南非夸祖鲁纳塔尔省,第二代 InSTI 用于治疗接受利福平治疗的结核病合并感染患者的 HIV-1
  • 批准号:
    10459435
  • 财政年份:
    2020
  • 资助金额:
    $ 81.73万
  • 项目类别:
Second Generation InSTIs for the Treatment of HIV-1 in patients with TB co-infection on Rifampicin-based Treatment in KwaZulu Natal, South Africa
在南非夸祖鲁纳塔尔省,第二代 InSTI 用于治疗接受利福平治疗的结核病合并感染患者的 HIV-1
  • 批准号:
    10829561
  • 财政年份:
    2020
  • 资助金额:
    $ 81.73万
  • 项目类别:
Mentoring Investigators in HIV and Tuberculosis Therapeutics Research
指导艾滋病毒和结核病治疗研究的研究人员
  • 批准号:
    9926650
  • 财政年份:
    2020
  • 资助金额:
    $ 81.73万
  • 项目类别:
Mentoring Investigators in HIV and Tuberculosis Therapeutics Research
指导艾滋病毒和结核病治疗研究的研究人员
  • 批准号:
    10729712
  • 财政年份:
    2020
  • 资助金额:
    $ 81.73万
  • 项目类别:
Second Generation InSTIs for the Treatment of HIV-1 in patients with TB co-infection on Rifampicin-based Treatment in KwaZulu Natal, South Africa
在南非夸祖鲁纳塔尔省,第二代 InSTI 用于治疗接受利福平治疗的结核病合并感染患者的 HIV-1
  • 批准号:
    10677030
  • 财政年份:
    2020
  • 资助金额:
    $ 81.73万
  • 项目类别:
Mentoring Investigators in HIV and Tuberculosis Therapeutics Research
指导艾滋病毒和结核病治疗研究的研究人员
  • 批准号:
    10335264
  • 财政年份:
    2020
  • 资助金额:
    $ 81.73万
  • 项目类别:
Second Generation InSTIs for the Treatment of HIV-1 in patients with TB co-infection on Rifampicin-based Treatment in KwaZulu Natal, South Africa
在南非夸祖鲁纳塔尔省,第二代 InSTI 用于治疗接受利福平治疗的结核病合并感染患者的 HIV-1
  • 批准号:
    10840501
  • 财政年份:
    2020
  • 资助金额:
    $ 81.73万
  • 项目类别:
Second Generation InSTIs for the Treatment of HIV-1 in patients with TB co-infection on Rifampicin-based Treatment in KwaZulu Natal, South Africa
在南非夸祖鲁纳塔尔省,第二代 InSTI 用于治疗接受利福平治疗的结核病合并感染患者的 HIV-1
  • 批准号:
    10226892
  • 财政年份:
    2020
  • 资助金额:
    $ 81.73万
  • 项目类别:
Ph2a Study: Rifampin, Merrem, Augmentin for Tuberculosis IND 129159; 12/31/2015
Ph2a 研究:利福平、Merrem、Augmentin 治疗结核病 IND 129159;
  • 批准号:
    10014610
  • 财政年份:
    2017
  • 资助金额:
    $ 81.73万
  • 项目类别:

相似海外基金

Pharmacy-led Transitions of Care Intervention to Address System-Level Barriers and Improve Medication Adherence in Socioeconomically Disadvantaged Populations
药房主导的护理干预转型,以解决系统层面的障碍并提高社会经济弱势群体的药物依从性
  • 批准号:
    10594350
  • 财政年份:
    2023
  • 资助金额:
    $ 81.73万
  • 项目类别:
Evaluating Centralizing Interventions to Address Low Adherence to Lung Cancer Screening Follow-up in Decentralized Settings
评估集中干预措施,以解决分散环境中肺癌筛查随访依从性低的问题
  • 批准号:
    10738120
  • 财政年份:
    2023
  • 资助金额:
    $ 81.73万
  • 项目类别:
Suubi-Mhealth: A mobile health intervention to address depression and improve ART adherence among Youth living with HIV (YLHIV) in Uganda
Suubi-Mhealth:一种移动健康干预措施,旨在解决乌干达艾滋病毒感染者 (YLHIV) 青少年的抑郁症问题并提高抗逆转录病毒疗法的依从性
  • 批准号:
    10526768
  • 财政年份:
    2022
  • 资助金额:
    $ 81.73万
  • 项目类别:
Suubi-Mhealth: A mobile health intervention to address depression and improve ART adherence among Youth living with HIV (YLHIV) in Uganda
Suubi-Mhealth:一种移动健康干预措施,旨在解决乌干达艾滋病毒感染者 (YLHIV) 青少年的抑郁症问题并提高抗逆转录病毒疗法的依从性
  • 批准号:
    10701072
  • 财政年份:
    2022
  • 资助金额:
    $ 81.73万
  • 项目类别:
A behavioral intervention for Black men who have sex with men and live with HIV to address intersectional stigma and improve antiretroviral therapy adherence
针对男男性行为且感染艾滋病毒的黑人男性进行行为干预,以解决交叉耻辱并提高抗逆转录病毒治疗的依从性
  • 批准号:
    10679092
  • 财政年份:
    2021
  • 资助金额:
    $ 81.73万
  • 项目类别:
A behavioral intervention for Black men who have sex with men and live with HIV to address intersectional stigma and improve antiretroviral therapy adherence
针对男男性行为且感染艾滋病毒的黑人男性进行行为干预,以解决交叉耻辱并提高抗逆转录病毒治疗的依从性
  • 批准号:
    10432133
  • 财政年份:
    2021
  • 资助金额:
    $ 81.73万
  • 项目类别:
A behavioral intervention for Black men who have sex with men and live with HIV to address intersectional stigma and improve antiretroviral therapy adherence
针对男男性行为且感染艾滋病毒的黑人男性进行行为干预,以解决交叉耻辱并提高抗逆转录病毒治疗的依从性
  • 批准号:
    10327065
  • 财政年份:
    2021
  • 资助金额:
    $ 81.73万
  • 项目类别:
Leveraging Technology to Address Access and Adherence to Conventional Hospital-Based Pulmonary Rehabilitation in Veterans with COPD
利用技术解决慢性阻塞性肺病退伍军人接受和坚持传统医院肺康复的问题
  • 批准号:
    10377366
  • 财政年份:
    2019
  • 资助金额:
    $ 81.73万
  • 项目类别:
Leveraging Technology to Address Access and Adherence to Conventional Hospital-Based Pulmonary Rehabilitation in Veterans with COPD
利用技术解决慢性阻塞性肺病退伍军人接受和坚持传统医院肺康复的问题
  • 批准号:
    10574496
  • 财政年份:
    2019
  • 资助金额:
    $ 81.73万
  • 项目类别:
Targeted interventions to address the multi-level effects of gender-based violence on PrEP uptake and adherence among adolescent girls and young women in Kenya
有针对性的干预措施,以解决性别暴力对肯尼亚少女和年轻妇女接受和坚持 PrEP 的多层面影响
  • 批准号:
    9403567
  • 财政年份:
    2017
  • 资助金额:
    $ 81.73万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了