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
- 来源:
- 关键词:Acquired Immunodeficiency SyndromeAddressAdherenceAffectAntitubercular AgentsBacteriaBiologicalBiological Response Modifier TherapyBloodCOVID-19Cessation of lifeClinicalCohort StudiesCollaborationsCollectionComplementDNADatabasesDiseaseDoseDrug ExposureDrug InteractionsDrug KineticsDrug TargetingDrug resistanceDrug resistance in tuberculosisDrynessEnrollmentEpidemiologyExposure toFailureFundingGenesGenetic PolymorphismGenotypeGeographyGoalsHIVHIV/TBHairHealthIndividualInflammationIntermediate resistanceInternationalKnowledgeLungLung diseasesMeasuresMediatingMinority GroupsModelingMutationMycobacterium tuberculosisOutcomeParticipantPatient-Focused OutcomesPatientsPersonsPharmaceutical PreparationsPharmacodynamicsPlayPreventionPulmonary TuberculosisPyrazinamideRecurrenceRelapseResearchResearch DesignResearch PersonnelResistanceRifampinRiskRoleSamplingScience EnrichmentSentinelSiteSpottingsSputumToxic effectTreatment FailureTreatment outcomeTuberculosisUnited States National Institutes of HealthViremiaWorkacquired drug resistancecare outcomesco-infectioncohortdesignexperiencefollow-upgenome sequencinghigh riskimprovedisoniazidlung healthlung injurymortalitypatient populationpharmacokinetics and pharmacodynamicspharmacometricspillprospectiveresistance mutationrespiratoryrespiratory healthsociodemographic factorssociodemographicstherapeutic targettreatment responsetuberculosis drugstuberculosis treatmentwhole genome
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.
项目总结
结核病是仅次于新冠肺炎的全球主要死亡传染病。结核病与艾滋病毒相互作用
在协同作用下,每一方都会恶化另一方的结果。结核病治疗不利的关键驱动因素
结果是接触不到最理想的药物。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以下疾病所需的累积暴露阈值
抵抗的出现没有被定义,特别是在方案环境中。在我们题为
“调查结核病-艾滋病毒(ImPPRove TB-HIV)的多种PK和PD关系”,我们将利用
结核病哨兵研究网络(TB SRN),一个协调的全球大型平台队列研究
在感染和不感染艾滋病毒的肺结核病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区域进行
药代动力学-药效学(PK-PD)分析,采用嵌套病例队列设计。我们将衡量
通过收集干血点(DB)进行个人PK,这些血点易于收集、存储和运输,以及
头发中的累积药物暴露,这既反映了依从性,也反映了PK。在目标1(PK-PD目标)中,我们将
检查结核病药物PK和累积药物暴露对结核病治疗不利风险的影响
感染或不感染艾滋病毒的肺结核病患者的结果(死亡、失败、复发)。在AIM 2
(PK-耐药性目标),我们将调查药物暴露对结核病耐药性出现的影响
突变。在目标3(PK-肺健康目标)中,我们将评估抗结核药物暴露之间的关系
以及结核病后肺部疾病和纵向肺健康。因此,IMPPRove研究旨在阐明
药物暴露与不利的结核病治疗结果、较差的肺部健康以及
在考虑到艾滋病毒状况的情况下,在大量多国患者人口中的现场条件下的耐药性
以及其他已知的影响这些结果的因素。目标是为结核病治疗的优化提供信息(右
剂量,正确的患者),以改善对患者具有临床重要性的结果。
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)
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Kelly E. Dooley其他文献
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
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
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
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
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
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{{ truncateString('Kelly E. Dooley', 18)}}的其他基金
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:
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