Reservoir features associated with time-to-rebound during analytical treatment interruption
与分析处理中断期间的反弹时间相关的储层特征
基本信息
- 批准号:10614027
- 负责人:
- 金额:$ 39.51万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-05-01 至 2027-04-30
- 项目状态:未结题
- 来源:
- 关键词:AcuteAffectAgonistBackBindingBioinformaticsBiological AssayCellsChronicChronic PhaseClinical TrialsCombined Modality TherapyDiagnosisDrug or chemical Tissue DistributionEarly treatmentEventFoundationsFundingGenetic TranscriptionGenomeHIVHIV therapyImmuneIndividualInfectionInterruptionInterventionKnowledgeLeukapheresisMeasurementMethodsMonitorNatureParticipantPatientsPersonsPhenotypePlasmaPropertyProvirusesRNARecrudescencesSamplingSourceSpecimenTechniquesTechnologyTestingTimeTranscriptVaccine TherapyViralViral reservoirViremiaVirusacute infectionantiretroviral therapychimeric antigen receptor T cellschronic infectioncohortgenome sequencinghigh dimensionalityimmunoregulationintervention effectmortalitynovelsingle cell analysissingle-cell RNA sequencingtoolviral rebound
项目摘要
Project Summary/Abstract (Project 3)
Combination antiretroviral therapy (ART) can suppress HIV replication and lead to decreased mortality
in HIV-infected individuals. However, ART does not eliminate the reservoir of HIV-infected cells, and upon
treatment interruption or cessation, virus typically rebounds from this reservoir within several weeks. Although
the viral reservoir has long been recognized as the main barrier to curing HIV, the basic mechanisms underlying
viral rebound, and the nature of the rebound-competent reservoir cells, remain poorly understood. In this Project,
we hypothesize that both viral transcriptionally activity and immune states of reservoir cells are key determinants
of the time it takes for virus to rebound when ART is stopped, and that these features will define the early targets
of infection at the time of rebound. To test this hypothesis, we will implement a variety of high-dimensional single-
cell analysis techniques to define the HIV transcriptional state and phenotypic features of HIV reservoir cells in
people living with HIV (PLWH) undergoing analytical treatment interruption (ATI) as part of ongoing trials. These
include individuals who initiated treatment early after diagnosis (Fiebigs I-V of acute infection) and those who
initiated treatment during the chronic phase of infection. In Aim 1, ddPCR- and viral sequencing-based
approaches will be used to characterize the intactness and HIV transcriptional activity of reservoir cells, while
novel single-cell methods will be used to interrogate the phenotypes of transcriptionally-active and inducible
reservoir cells. This information will then be associated with the time it takes virus to rebound from these
individuals. These same individuals will be extensively sampled over the course of treatment interruption in order
to better understand the early events occurring at the time of rebound, which will be extensively characterized in
Aim 2. Finally, Aim 3 will use similar techniques to characterize two additional cohorts of individuals undergoing
ATI, but in the context of cure-based interventions aimed at achieving a functional cure through immune
modulation. Overall, this study will establish an in-depth view of the viral and host cell features of rebound-
competent reservoir cells, and will relate this knowledge to the time it takes for viral rebound during ART
interruption, in the context of ongoing non-interventional and interventional cure-based clinical trials.
项目概要/摘要(项目3)
联合抗逆转录病毒疗法(ART)可以抑制HIV复制,降低死亡率
在HIV感染者身上。然而,ART并不能消除HIV感染细胞的储存库,
治疗中断或停止后,病毒通常在几周内从该储库反弹。虽然
长期以来,病毒储存库一直被认为是治疗HIV的主要障碍,其基本机制是
病毒反弹和具有反弹能力的储库细胞的性质仍然知之甚少。在本项目中,
我们假设病毒的转录活性和储库细胞的免疫状态都是关键的决定因素,
当ART停止时病毒反弹所需的时间,这些特征将确定早期目标
在反弹的时候感染。为了验证这一假设,我们将实现各种高维单-
细胞分析技术,以确定艾滋病毒的转录状态和表型特征的艾滋病毒水库细胞,
作为正在进行的试验的一部分,正在接受分析性治疗中断(ATI)的艾滋病毒感染者(PLWH)。这些
包括在诊断后早期开始治疗的个体(急性感染的Fiebigs I-V)和
在感染的慢性阶段开始治疗。在目标1中,基于ddPCR和病毒测序的
方法将用于表征储库细胞的完整性和HIV转录活性,
新的单细胞方法将用于询问转录活性和诱导型的表型。
储库细胞然后,这些信息将与病毒从这些位置反弹所需的时间相关联。
个体在治疗中断期间,将对这些相同的个体进行广泛采样,
为了更好地了解在反弹时发生的早期事件,这将广泛地表现在
目标2.最后,Aim 3将使用类似的技术来描述另外两个接受治疗的个体队列,
ATI,但在治疗为基础的干预,旨在实现功能性治愈,通过免疫治疗的背景下,
调变总的来说,这项研究将建立一个深入的看法,病毒和宿主细胞的特点反弹-
并将这些知识与ART期间病毒反弹所需的时间联系起来
在正在进行的非干预性和干预性治疗临床试验的背景下中断。
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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Nadia R Roan其他文献
Transient Anti-Interferon Auto Antibodies in the Airway Are Associated with Recovery in Mild COVID-19
- DOI:
10.1182/blood-2023-190358 - 发表时间:
2023-11-02 - 期刊:
- 影响因子:
- 作者:
Benjamin R Babcock;Astrid Kosters;Nadia R Roan;Sulggi Lee;Eliver E.B. Ghosn - 通讯作者:
Eliver E.B. Ghosn
Nadia R Roan的其他文献
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{{ truncateString('Nadia R Roan', 18)}}的其他基金
Reservoir features associated with time-to-rebound during analytical treatment interruption
与分析处理中断期间的反弹时间相关的储层特征
- 批准号:
10459934 - 财政年份:2022
- 资助金额:
$ 39.51万 - 项目类别:
Characterizing ART-free NK cell-mediated control of HIV infection in people living with HIV
描述 HIV 感染者中无 ART 的 NK 细胞介导的 HIV 感染控制
- 批准号:
10535192 - 财政年份:2022
- 资助金额:
$ 39.51万 - 项目类别:
Characterizing ART-free NK cell-mediated control of HIV infection in people living with HIV
描述 HIV 感染者中无 ART 的 NK 细胞介导的 HIV 感染控制
- 批准号:
10671559 - 财政年份:2022
- 资助金额:
$ 39.51万 - 项目类别:
Phenotypic and mechanistic analysis of the in vivo HIV latent reservoir by single-cell technologies
通过单细胞技术对体内 HIV 潜伏病毒库进行表型和机制分析
- 批准号:
10357547 - 财政年份:2019
- 资助金额:
$ 39.51万 - 项目类别:
Phenotypic and mechanistic analysis of the in vivo HIV latent reservoir by single-cell technologies
通过单细胞技术对体内 HIV 潜伏病毒库进行表型和机制分析
- 批准号:
10448398 - 财政年份:2019
- 资助金额:
$ 39.51万 - 项目类别:
Phenotypic and mechanistic analysis of the in vivo HIV latent reservoir by single-cell technologies
通过单细胞技术对体内 HIV 潜伏病毒库进行表型和机制分析
- 批准号:
10360854 - 财政年份:2019
- 资助金额:
$ 39.51万 - 项目类别:
Project 1: Using CyTOF to identify phenotypic and functional biomarkers predicting time to HIV rebound after treatment interruption
项目 1:使用 CyTOF 识别表型和功能生物标志物,预测治疗中断后 HIV 反弹的时间
- 批准号:
10223995 - 财政年份:2017
- 资助金额:
$ 39.51万 - 项目类别:
Exploiting the Host-HIV Interface To Identify Biomarkers Predicting Time to Viral Rebound after Treatment Interruption
利用宿主-HIV 界面识别生物标志物,预测治疗中断后病毒反弹的时间
- 批准号:
10223991 - 财政年份:2017
- 资助金额:
$ 39.51万 - 项目类别:
Characterization of Exosomes From Semen of Uninfected and HIV-Infected Men
未感染和 HIV 感染男性精液中外泌体的表征
- 批准号:
9228315 - 财政年份:2016
- 资助金额:
$ 39.51万 - 项目类别:
Characterization of Exosomes From Semen of Uninfected and HIV-Infected Men
未感染和 HIV 感染男性精液中外泌体的表征
- 批准号:
9062790 - 财政年份:2016
- 资助金额:
$ 39.51万 - 项目类别:
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