Sex-differences in HIV persistence and Immune Dynamics during Reproductive Aging
生殖衰老过程中艾滋病毒持久性和免疫动态的性别差异
基本信息
- 批准号:10838316
- 负责人:
- 金额:$ 83.95万
- 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:2023-09-22 至 2028-07-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAftercareAgeAgingAlgorithmsAntibodiesAreaAutomobile DrivingBar CodesBioinformaticsBiologicalBiological AssayBiometryBlood CellsCD4 Positive T LymphocytesCD8B1 geneCell SurvivalClinicalClinical DataClonal ExpansionCohort StudiesCollaborationsCytokine Network PathwayDNADataDetectionEstradiolEstrogen declineEstrogensExclusionFutureGene ExpressionGene Expression ProfileGenesGenetic TranscriptionGoalsGonadal Steroid HormonesHIVHIV InfectionsHLA-DR AntigensHormonesIL7 geneImmuneImmune responseImmunologicsImmunologyImmunophenotypingInfectionInflammationInflammatoryInflammatory ResponseInflammatory Response PathwayInterferon Type IIKnowledgeMeasuresMediatingNatural HistoryNatural Killer CellsOutcomeParticipantPathogenesisPathway interactionsPerimenopausePeripheralPilot ProjectsPlasmaPostmenopausePremenopauseProcessProductivityProliferatingProtocols documentationRNARaceRecording of previous eventsRepressionResearchRoleSamplingSeriesSex DifferencesSignal TransductionSiteSpecimenStandardizationStatistical Data InterpretationT-Cell ActivationTestingThe Multicenter AIDS Cohort StudyTherapeuticTimeTranscriptTranscriptional RegulationViremiaWomanWomen&aposs Interagency HIV StudyWorkantiretroviral therapybiobankcis-femalecis-malecohortcytokinedesignexperienceexperimental studyhuman subjectimmune activationimmunological interventionimprovedinclusion criteriainflammatory markerinsightintegration sitelongitudinal designmalemenmiddle agemonocytemultimodal datanovelreproductivereproductive senescenceresponsesexsingle cell sequencingsingle-cell RNA sequencingtime intervaltranscriptomicsvirology
项目摘要
ABSTRACT
Background. Sex-based differences, largely controlled by sex hormones, affect the natural and treated history
of HIV infection and HIV-specific immune responses. Our previous work has shown that estrogen potently
represses HIV transcription, thus decreasing cellular HIV RNA in women compared to men. Unexpectedly,
women undergoing reproductive aging have a progressive increase in levels of inducible HIV reservoir, while
estrogen declines. This observed expansion of the reservoir as women age is in sharp contrast to the steady
decline in the reservoir size observed in men. Given the increasing number of women aging with HIV, it is critical
to determine the interplay of HIV persistence and declining sex hormones during reproductive aging to design
effective HIV cure strategies.
Our goal. Our study is specifically designed with samples from both cisgender men and women across the
reproductive aging spectrum. We will first define the impact of reproductive aging on multiple features of the
reservoir including size, transcriptional activity, along with a novel exploration of clonal expansion (Aim 1). Next,
we will precisely define the immunologic changes over the course of reproductive aging, using single cell
sequencing combined with immunophenotyping using DNA-barcoded antibodies (Aim 2). The data will be
integrated, and key features established using advanced statistical analyses.
Study Cohort: Longitudinal samples (viable cells, plasma), collected, processed, and stored using standardized
protocols in the multi-site Women's Interagency HIV Study (WIHS) and Multicenter AIDS Cohort Study (MACS)
cohorts will be utilized for all proposed experiments. First, we will carefully select 25 cisgender WWH on
suppressive combination antiretroviral therapy (ART) with biologic samples representing four reproductive
stages (reproductive/pre-menopause, menopausal transition/early and late perimenopause, post-menopause).
Then, we will identify 25 MWH as controls using a multivariate propensity score based matching algorithm. After
matching, stored samples collected between 2009 and 2019 will be selected based on similar time-intervals
across both groups.
How will we advance the field? To date, the majority of HIV cure research has used male participants and
therefore a significant knowledge gap exists between men and women. We do not know if the same immune-
modulatory interventions will be effective in promoting HIV RNA transcription in men and women and how
declining sex hormones will impact their efficacy. Agents that are designed for “kick and kill” strategies may be
impacted by estradiol-mediated mechanisms as women undergo reproductive aging. A better understanding of
these differences will assist in the design of future cure approaches that can be applied across sexes.
摘要
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 }}
Sara Gianella Weibel其他文献
Sara Gianella Weibel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('Sara Gianella Weibel', 18)}}的其他基金
Impact of Reproductive Aging On HIV Persistence and Inflammation
生殖衰老对艾滋病毒持续性和炎症的影响
- 批准号:
10433074 - 财政年份:2021
- 资助金额:
$ 83.95万 - 项目类别:
Mechanisms of CMV Replication on HIV Persistence
CMV 复制对 HIV 持续存在的机制
- 批准号:
10012877 - 财政年份:2020
- 资助金额:
$ 83.95万 - 项目类别:
The HIV-associated Opioid Micro-Environment (HOME) Project
HIV 相关阿片类药物微环境 (HOME) 项目
- 批准号:
10056153 - 财政年份:2020
- 资助金额:
$ 83.95万 - 项目类别:
Mechanisms of CMV Replication on HIV Persistence
CMV 复制对 HIV 持续存在的机制
- 批准号:
10241944 - 财政年份:2020
- 资助金额:
$ 83.95万 - 项目类别:
Mechanisms of CMV Replication on HIV Persistence
CMV 复制对 HIV 持续存在的机制
- 批准号:
10448351 - 财政年份:2020
- 资助金额:
$ 83.95万 - 项目类别:
Effect of Declining Sex Hormones on HIV persistence in HIV Infected Women on ART
性激素下降对接受 ART 的 HIV 感染妇女中 HIV 持续存在的影响
- 批准号:
9568360 - 财政年份:2017
- 资助金额:
$ 83.95万 - 项目类别:
Effect of Declining Sex Hormones on HIV persistence in HIV Infected Women on ART
性激素下降对接受 ART 的 HIV 感染妇女中 HIV 持续存在的影响
- 批准号:
9482258 - 财政年份:2017
- 资助金额:
$ 83.95万 - 项目类别:
相似海外基金
Life outside institutions: histories of mental health aftercare 1900 - 1960
机构外的生活:1900 - 1960 年心理健康善后护理的历史
- 批准号:
DP240100640 - 财政年份:2024
- 资助金额:
$ 83.95万 - 项目类别:
Discovery Projects
Development of a program to promote psychological independence support in the aftercare of children's homes
制定一项计划,促进儿童之家善后护理中的心理独立支持
- 批准号:
23K01889 - 财政年份:2023
- 资助金额:
$ 83.95万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Integrating Smoking Cessation in Tattoo Aftercare
将戒烟融入纹身后护理中
- 批准号:
10452217 - 财政年份:2022
- 资助金额:
$ 83.95万 - 项目类别:
Integrating Smoking Cessation in Tattoo Aftercare
将戒烟融入纹身后护理中
- 批准号:
10670838 - 财政年份:2022
- 资助金额:
$ 83.95万 - 项目类别:
Aftercare for young people: A sociological study of resource opportunities
年轻人的善后护理:资源机会的社会学研究
- 批准号:
DP200100492 - 财政年份:2020
- 资助金额:
$ 83.95万 - 项目类别:
Discovery Projects
Creating a National Aftercare Strategy for Survivors of Pediatric Cancer
为小儿癌症幸存者制定国家善后护理策略
- 批准号:
407264 - 财政年份:2019
- 资助金额:
$ 83.95万 - 项目类别:
Operating Grants
Aftercare of green infrastructure: creating algorithm for resolving human-bird conflicts
绿色基础设施的善后工作:创建解决人鸟冲突的算法
- 批准号:
18K18240 - 财政年份:2018
- 资助金额:
$ 83.95万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Development of an aftercare model for children who have experienced invasive procedures
为经历过侵入性手术的儿童开发善后护理模型
- 批准号:
17K12379 - 财政年份:2017
- 资助金额:
$ 83.95万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of a Comprehensive Aftercare Program for children's self-reliance support facility
为儿童自力更生支持设施制定综合善后护理计划
- 批准号:
17K13937 - 财政年份:2017
- 资助金额:
$ 83.95万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Project#2 Extending Treatment Effects Through an Adaptive Aftercare Intervention
项目
- 批准号:
8742767 - 财政年份:2014
- 资助金额:
$ 83.95万 - 项目类别: