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

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.
项目总结

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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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

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{{ 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:

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