STI and Implications for HIV Transmission and Prevention

性传播感染以及对艾滋病毒传播和预防的影响

• 批准号: 9334534
• 负责人: Colleen F Kelley
• 金额: $ 46.6万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9334534
• 关键词: AIDS prevention; Adult; Aftercare; Anus; Area; Biopsy; Biopsy Specimen; Cells; Chlamydia; Clinical Research; Data; Development; Effectiveness; Enrollment; Exposure to; Family; Flow Cytometry; Gonorrhea; HIV; HIV Infections; HIV Seropositivity; Hyaluronidase; Immune; Immune response; Immunohistochemistry; Immunology; Incidence; Infection; Infection prevention; Infiltration; Inflammation; Inflammatory; Injury; Latent Syphilis; Matrix Metalloproteinases; Mucositis; Mucous Membrane; Neutrophil Infiltration; Organism; Physiological; Population; Predisposition; Prevention; Preventive Intervention; Recruitment Activity; Rectum; Research; Research Infrastructure; Resolution; Role; Sampling; Sexually Transmitted Diseases; Syphilis; Time; Vaccines; Viral Load result; Woman; Work; adolescent men who have sex with men; aged; antiretroviral therapy; cohort; cytokine; design; experimental study; high risk; improved; inflammatory marker; mRNA Expression; men; men who have sex with men; men' s group; microbiome; microbiota; molecular marker; next generation sequencing; nonhuman primate; programs; rectal; screening; transcriptome; transmission process; treatment duration; vaginal transmission; young men who have sex with men

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. However, the majority of HIV mucosal transmission research has concentrated on vaginal transmission in women and non-human primates, which is then extrapolated to understanding the mechanisms of rectal transmission among MSM. In addition, the role of inflammation in the rectal mucosa attributed to bacterial sexually transmitted infections (STI), including Chlamydia (CT), Gonorrhea (GC), and syphilis, has been understudied to date despite the tremendous burden of STI in MSM and their influence on HIV transmission. We have previously shown that rectal STI, even in the setting of routine screening and treatment, is associated with HIV seroconversion in a cohort of HIV-negative MSM. For HIV positive MSM, our prior work shows that rectal shedding of HIV remains low in men on suppressive antiretroviral therapy (ART) with rectal GC and/or CT; however, sampling of the mucosa was not optimal to detect low level shedding in this study. In the absence of rectal STI, preliminary data presented in this application with adult HIV-negative MSM aged 18-45 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 rectal mucosal studies of MSM to examine the effect of bacterial STI on the rectal mucosal resident cellular populations (aim1) and the microbiome (aim2). In aim 3, we will study resolution of inflammation after treatment of STI and its effect on ex vivo HIV infection of the rectal mucosa. 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 the host response to STI in the rectum will be useful to the design of biomedical HIV and bacterial STI prevention mechanisms, including effective vaccines.

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 被认为发生在 MSM 中。然而，大多数 HIV 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，然后推断为 了解 MSM 之间的直肠传播机制。此外，炎症在 直肠粘膜归因于细菌性传播感染 (STI)，包括衣原体 (CT)、淋病 (GC) 和梅毒，尽管性传播感染给 MSM 带来了巨大的负担，但迄今为止尚未得到充分研究。 对艾滋病毒传播的影响。我们之前已经表明，直肠性传播感染，即使是在常规情况下 筛查和治疗与 HIV 阴性 MSM 人群中的 HIV 血清转化相关。对于艾滋病毒 阳性男男性行为者，我们之前的工作表明，在接受抑制性治疗的男性中，直肠艾滋病毒排出量仍然较低 使用直肠 GC 和/或 CT 进行抗逆转录病毒治疗 (ART)；然而，粘膜取样并不是最佳选择 在本研究中检测低水平脱落。在没有直肠性传播感染的情况下，本报告中提供的初步数据 18-45 岁成人 HIV 阴性 MSM 的应用显示出独特的先天性和适应性促炎作用 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，我们建议扩大 MSM 的直肠粘膜研究，以检查 细菌性传播感染对直肠粘膜驻留细胞群 (aim1) 和微生物群 (aim2) 的影响。在 目标3，我们将研究STI治疗后炎症的消退及其对体外HIV感染的影响 直肠粘膜。我们将在我们成功的转化粘膜免疫学计划的基础上，以高度的 成功的临床研究和保留基础设施旨在了解可能的因素 影响 MSM 之间的直肠传播。更好地了解宿主对直肠性传播感染的反应 将有助于设计生物医学艾滋病毒和细菌性传播感染预防机制，包括有效的 疫苗。