Understanding Rectal HIV transmission among At-risk MSM: Age, Intercourse, and Mucosal Injur
了解高危 MSM 中的直肠 HIV 传播:年龄、性交和粘膜损伤
基本信息
- 批准号:9245391
- 负责人:
- 金额:$ 63.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-01-24 至 2020-12-31
- 项目状态:已结题
- 来源:
- 关键词:AIDS preventionAbstinenceAdolescentAdultAgeAnal SexAnusAreaAttenuatedBiological AssayBiopsyBiopsy SpecimenCell ProliferationCellsClinical ResearchCoitusColumnar EpitheliumDataDevelopmentEffectivenessEnrollmentEnvironmentExhibitsExposure toFamilyFemaleFlow CytometryHIVHIV InfectionsHIV vaccineImage AnalysisImmuneImmune responseImmunohistochemistryImmunologicsImmunologyIncidenceInfectionInfiltrationInflammatoryInflammatory ResponseInjuryMeasuresMechanicsMucositisMucous MembraneNatural HistoryOutcomePhysiologicalPopulationPredispositionPreventive InterventionRecording of previous eventsRectumResearchResearch InfrastructureResolutionRiskSeminal fluidSex BehaviorSiteTimeTime StudyTraumaVaginaVariantWomanadolescent men who have sex with menage effectage relatedagedcohortcondomscytokinedesigndigital imagingexperimental studyfollow-uphealinghigh riskimprovedmenmen who have sex with menmen&aposs groupmicrobiotanext generation sequencingnonhuman primatepenisprogramsrectalreproductive tractresponsetranscriptometranscriptome sequencingtransmission processvaginal transmission
项目摘要
PROJECT SUMMARY
Despite making up only 2% of the US population, men who have sex with men (MSM) accounted for 67% of
new HIV infections in 2014, and incidence rates among adolescent MSM are alarmingly high in some areas.
One potential barrier to the effectiveness of biomedical HIV prevention interventions among MSM is the
physiologic efficiency of HIV transmission across the rectal mucosa, where approximately 70% of infections
are thought to occur among MSM, as compared to vaginal or penile transmission. However, the majority of HIV
mucosal transmission research has concentrated on vaginal transmission in women and non-human primates,
which is then extrapolated and applied to understanding the mechanisms of rectal transmission among MSM.
The rectal mucosa, with its single layer of columnar epithelium, is theoretically more prone to mechanical
trauma during sexual intercourse than the vagina or penis, and exposure to semen during coitus causes a pro-
inflammatory cascade in the female genital tract that may have similar effects in the rectum. In our preliminary
data with 41 adult HIV-negative MSM aged 18-45, we show a distinct innate and adaptive pro-inflammatory
immune response to condomless receptive anal intercourse (CRAI) in the rectal mucosa, and that the diversity
and composition of the rectal mucosal microbiota differ between adult MSM who engage in CRAI versus men
who do not engage in anal intercourse (AI) with MSM engaging in CRAI being enriched for the family
Prevotellaceae. In this application, we propose to expand our previous studies to examine how factors such as
age and episodic, frequent, consensual sexual activity can influence rectal transmission, and to determine
whether the mucosal inflammation associated with CRAI leads to delayed mucosal healing after injury. In Aim
1, we will compare the rectal mucosal immune milieu between adolescent MSM with recent anal sex debut,
adult MSM who have engaged in CRAI for > 5 years, and men who do not engage in AI with state of the art
flow cytometry, RNA-Seq, and microbiota sequencing assays and examine the ex vivo impact on HIV
susceptibility with rectal explant challenge experiments. In Aim 2, we will tease out the effects of rectal mucosal
trauma due to episodic anal intercourse with and without semen exposure in a cohort of adult MSM engaging
in CRAI. Finally, in aim 3, we will examine whether adult MSM who engage in CRAI exhibit delayed rectal
mucosal healing after experimentally induced injury with rectal biopsy during high resolution anoscopy with
follow-up digital imaging. We will build upon our successful translational mucosal immunology program with a
highly successful clinical research and retention infrastructure that was designed to understand factors that
may influence rectal transmission among MSM. A better understanding of rectal HIV transmission among MSM
will contribute valuable information to the development of biomedical HIV prevention interventions, including an
HIV vaccine.
项目概要
尽管男男性行为者 (MSM) 只占美国人口的 2%,但却占到了 67%。
2014年新增艾滋病感染者数,部分地区青少年男男性接触者发病率高得惊人。
MSM 中艾滋病毒生物医学预防干预措施有效性的一个潜在障碍是
HIV 通过直肠粘膜传播的生理效率,大约 70% 的感染是通过直肠粘膜传播的
与阴道或阴茎传播相比,该病被认为发生在 MSM 中。然而,大多数艾滋病毒
粘膜传播研究集中于女性和非人类灵长类动物的阴道传播,
然后进行推断并应用于了解 MSM 之间的直肠传播机制。
直肠粘膜具有单层柱状上皮,理论上更容易受到机械作用
性交过程中对阴道或阴茎的创伤大于阴道或阴茎,并且在性交过程中接触精液会导致亲
女性生殖道的炎症级联反应可能对直肠产生类似的影响。在我们的初步
通过对 41 名 18-45 岁成年 HIV 阴性 MSM 的数据分析,我们发现了独特的先天性和适应性促炎性
直肠粘膜对无套接受性肛交(CRAI)的免疫反应,以及多样性
参与 CRAI 的成年 MSM 与男性的直肠粘膜微生物群组成和组成存在差异
不与 MSM 进行肛交 (AI) 的人 参与 CRAI 使家庭更加丰富
普雷沃特拉科。在此应用中,我们建议扩展我们之前的研究,以研究诸如
年龄和间歇性、频繁的、双方同意的性活动可以影响直肠传播,并确定
与 CRAI 相关的粘膜炎症是否会导致损伤后粘膜愈合延迟。瞄准
1,我们将比较青少年 MSM 与最近首次肛交的直肠粘膜免疫环境,
从事 CRAI 5 年以上的成年 MSM,以及未从事最先进 AI 的男性
流式细胞术、RNA-Seq 和微生物群测序分析并检查对 HIV 的离体影响
直肠外植体激发实验的敏感性。在目标 2 中,我们将梳理直肠粘膜的影响
成年 MSM 群体中因有或没有精液暴露的偶发性肛交造成的创伤
在CRAI。最后,在目标 3 中,我们将检查参与 CRAI 的成年 MSM 是否表现出延迟直肠
高分辨率肛门镜检查期间直肠活检实验诱导损伤后的粘膜愈合
后续数字成像。我们将在我们成功的转化粘膜免疫学计划的基础上,
非常成功的临床研究和保留基础设施,旨在了解以下因素:
可能影响 MSM 之间的直肠传播。更好地了解 MSM 中的直肠 HIV 传播
将为艾滋病毒生物医学预防干预措施的发展提供宝贵的信息,包括
艾滋病毒疫苗。
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 }}
Colleen F Kelley其他文献
Safety, pharmacokinetics, and neutralisation activity of PGDM1400LS, a V2 specific HIV-1 broadly neutralising antibody, infused intravenously or subcutaneously in people without HIV-1 in the USA (HVTN 140/HPTN 101 part A): a first-in-human, phase 1 randomised trial
PGDM1400LS 是一种 V2 特异性 HIV-1 广泛中和抗体,在美国无 HIV-1 人群中静脉或皮下输注的安全性、药代动力学和中和活性(HVTN 140/HPTN 101 A 部分):一项首次人体、1 期随机试验
- DOI:
10.1016/s2352-3018(25)00012-8 - 发表时间:
2025-06-01 - 期刊:
- 影响因子:13.000
- 作者:
Kelly E Seaton;Carmen A Paez;Chenchen Yu;Shelly T Karuna;Theresa Gamble;Maurine D Miner;Jack Heptinstall;Lu Zhang;Fei Gao;Margaret Yacovone;Hans Spiegel;Julie B Dumond;Maija Anderson;Estelle Piwowar-Manning;Bonnie Dye;India Tindale;Lori Proulx-Burns;Meg Trahey;Simbarashe Takuva;Azwidihwi Takalani;Colleen F Kelley - 通讯作者:
Colleen F Kelley
Phase 1 Open-Label Dose Escalation Trial for the Development of a Human Bacillus Calmette-Guérin Challenge Model for Assessment of Tuberculosis Immunity In Vivo.
开发用于评估体内结核病免疫力的人类卡介苗挑战模型的第一阶段开放标签剂量递增试验。
- DOI:
10.1093/infdis/jiad441 - 发表时间:
2023 - 期刊:
- 影响因子:0
- 作者:
Azra Blazevic;Rachel L Edwards;Mei Xia;C. Eickhoff;Fahreta Hamzabegovic;Krystal A. Meza;Huan Ning;Jan Tennant;Karla J Mosby;James C Ritchie;Tigisty Girmay;Lilin Lai;Michele McCullough;Allison Beck;Colleen F Kelley;Srilatha Edupuganti;Sarah Kabbani;Wendy Buchanan;M. Makhene;Delia Voronca;Sami R. Cherikh;Johannes B. Goll;N. Rouphael;Mark J. Mulligan;D. Hoft - 通讯作者:
D. Hoft
Colleen F Kelley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('Colleen F Kelley', 18)}}的其他基金
Defining Sex-Specific Systemic and Gut Inflammatory Profiles in People Living with HIV
定义艾滋病毒感染者的性别特异性全身和肠道炎症特征
- 批准号:
10619980 - 财政年份:2023
- 资助金额:
$ 63.04万 - 项目类别:
Gender as a biological variable: transcriptomic analysis of rectal mucosal immune cells among transgender people
性别作为生物变量:变性人直肠粘膜免疫细胞的转录组分析
- 批准号:
10376886 - 财政年份:2021
- 资助金额:
$ 63.04万 - 项目类别:
Gender as a biological variable: transcriptomic analysis of rectal mucosal immune cells among transgender people
性别作为生物变量:变性人直肠粘膜免疫细胞的转录组分析
- 批准号:
10258036 - 财政年份:2021
- 资助金额:
$ 63.04万 - 项目类别:
Parrying the Pitfalls of PrEP: Preventing Premature PrEP Discontinuation and STIs among Young Black MSM
避开 PrEP 的陷阱:防止年轻黑人 MSM 过早停止 PrEP 和性传播感染
- 批准号:
9927385 - 财政年份:2020
- 资助金额:
$ 63.04万 - 项目类别:
Parrying the Pitfalls of PrEP: Preventing Premature PrEP Discontinuation and STIs among Young Black MSM
避开 PrEP 的陷阱:防止年轻黑人 MSM 过早停止 PrEP 和性传播感染
- 批准号:
10133150 - 财政年份:2020
- 资助金额:
$ 63.04万 - 项目类别:
Parrying the Pitfalls of PrEP: Preventing Premature PrEP Discontinuation and STIs among Young Black MSM
避开 PrEP 的陷阱:防止年轻黑人 MSM 过早停止 PrEP 和性传播感染
- 批准号:
10652666 - 财政年份:2020
- 资助金额:
$ 63.04万 - 项目类别:
Parrying the Pitfalls of PrEP: Preventing Premature PrEP Discontinuation and STIs among Young Black MSM
避开 PrEP 的陷阱:防止年轻黑人 MSM 过早停止 PrEP 和性传播感染
- 批准号:
10399433 - 财政年份:2020
- 资助金额:
$ 63.04万 - 项目类别:
Understanding the rectal mucosal effects of cross-sex hormone therapy among US and Thai transgender women
了解跨性别激素治疗对美国和泰国变性女性直肠粘膜的影响
- 批准号:
10672350 - 财政年份:2019
- 资助金额:
$ 63.04万 - 项目类别:
Understanding the rectal mucosal effects of cross-sex hormone therapy among US and Thai transgender women
了解跨性别激素治疗对美国和泰国变性女性直肠粘膜的影响
- 批准号:
10227723 - 财政年份:2019
- 资助金额:
$ 63.04万 - 项目类别:
Understanding the rectal mucosal effects of cross-sex hormone therapy among US and Thai transgender women
了解跨性别激素治疗对美国和泰国变性女性直肠粘膜的影响
- 批准号:
10447095 - 财政年份:2019
- 资助金额:
$ 63.04万 - 项目类别:
相似海外基金
StuDy AimED at Increasing AlCohol AbsTinEnce (DEDICATE)
旨在提高酒精戒断率的研究(奉献)
- 批准号:
10577022 - 财政年份:2023
- 资助金额:
$ 63.04万 - 项目类别:
A Controlled Study of Extended Cannabis Abstinence in Major Depression
重度抑郁症患者长期吸食大麻的对照研究
- 批准号:
478313 - 财政年份:2023
- 资助金额:
$ 63.04万 - 项目类别:
Operating Grants
Exercised-induced modulation of insular cortex microcircuitry during alcohol abstinence
戒酒期间运动诱导的岛叶皮质微电路调节
- 批准号:
10748763 - 财政年份:2023
- 资助金额:
$ 63.04万 - 项目类别:
Prapela™ SVS: A cost-effective stochastic vibrotactile stimulation device toimprove the clinical course of infants with neonatal abstinence syndrome.
Prapela™ SVS:一种经济高效的随机振动触觉刺激装置,可改善患有新生儿戒断综合征的婴儿的临床过程。
- 批准号:
10837421 - 财政年份:2023
- 资助金额:
$ 63.04万 - 项目类别:
Enforced alcohol abstinence: does it reduce reoffending?
强制戒酒:会减少再犯罪吗?
- 批准号:
ES/X003566/1 - 财政年份:2023
- 资助金额:
$ 63.04万 - 项目类别:
Fellowship
Neurobiological impact of acute digital media abstinence among drug using college students
吸毒大学生急性数字媒体戒断的神经生物学影响
- 批准号:
10677380 - 财政年份:2023
- 资助金额:
$ 63.04万 - 项目类别:
Single-cell whole brain imaging of nicotine intoxication, dependence, and abstinence
尼古丁中毒、依赖和戒断的单细胞全脑成像
- 批准号:
10588509 - 财政年份:2023
- 资助金额:
$ 63.04万 - 项目类别:
Understanding recovery from alcohol use disorder: Longitudinal observation of two voluntary temporary abstinence periods
了解酒精使用障碍的恢复:两个自愿临时戒酒期的纵向观察
- 批准号:
10740677 - 财政年份:2023
- 资助金额:
$ 63.04万 - 项目类别:
Sleep Disturbances During Cocaine Abstinence, Dopamine Adaptations, and Motivation for Cocaine
可卡因戒断期间的睡眠障碍、多巴胺适应和可卡因动机
- 批准号:
10681668 - 财政年份:2023
- 资助金额:
$ 63.04万 - 项目类别:
Transcriptional adaptations driving the intensification of alcohol-seeking in dependent rats undergoing prolonged abstinence
转录适应导致长期戒酒的依赖性大鼠对酒精的渴求加剧
- 批准号:
10540014 - 财政年份:2022
- 资助金额:
$ 63.04万 - 项目类别: