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.
项目摘要/摘要(项目3)
联合抗逆转录病毒疗法(ART)可以抑制艾滋病毒复制并降低死亡率
在感染艾滋病毒的人身上。然而,抗逆转录病毒疗法并不能消除艾滋病毒感染细胞的储存库,而且在
如果治疗中断或停止,病毒通常会在几周内从这个蓄水池反弹。虽然
长期以来,病毒库一直被认为是治愈艾滋病毒的主要障碍,这是
病毒反弹,以及反弹能力强的储藏细胞的性质,仍然知之甚少。在这个项目中,
我们假设病毒转录活性和存储细胞的免疫状态都是关键决定因素。
当ART停止时,病毒反弹所需的时间,以及这些特征将定义早期目标
在反弹时感染的可能性。为了验证这一假设,我们将实现各种高维的单维-
用细胞分析技术确定艾滋病病毒储存细胞的转录状态和表型特征
作为正在进行的试验的一部分,艾滋病毒携带者(PLWH)正在接受分析治疗中断(ATI)。这些
包括确诊后早期开始治疗的个人(急性感染的Fiebigs I-V)和那些
在感染的慢性期开始治疗。在目标1中,基于ddPCR和病毒测序
方法将被用来表征储存细胞的完整性和艾滋病毒转录活性,而
新的单细胞方法将被用来询问转录活性和可诱导的表型
储集层细胞。这些信息将与病毒从这些病毒反弹所需的时间相关联
个人。这些人将在治疗中断的过程中按顺序广泛抽样
为了更好地了解反弹时发生的早期事件,将在
目标2。最后,目标3将使用类似的技术来描述另外两组正在接受
ATI,但在旨在通过免疫实现功能性治愈的基于治愈的干预措施的背景下
调制。总体而言,这项研究将深入了解反弹的病毒和宿主细胞特征-
并将这一知识与ART期间病毒反弹所需的时间联系起来
中断,在正在进行的非干预性和干预性基于治愈的临床试验的背景下。
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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