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.

项目摘要 尽管仅占美国人口的2％，但与男性发生性关系的男性占67％ 2014年的新艾滋病毒感染，青少年MSM的发病率在某些地区令人震惊。 MSM中生物医学艾滋病毒预防干预措施有效性的一个潜在障碍是 跨直肠粘膜的HIV传播的生理效率，其中约70％的感染 被认为发生在MSM之间。但是，大多数HIV粘膜传播研究具有 集中于女性和非人类灵长类动物的阴道传播，然后将其推断为 了解MSM之间直肠传播的机制。另外，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STI在MSM及其 对艾滋病毒传播的影响。我们以前已经表明，即使在例程的情况下，直肠性传播疾病 筛查和治疗与HIV阴性MSM队列中的HIV血清转化有关。艾滋病毒 正面MSM，我们先前的工作表明，在抑制性的男性中，艾滋病毒的直肠脱落仍然很低 直肠GC和/或CT的抗逆转录病毒疗法（ART）；但是，粘膜的抽样不是最佳的 在这项研究中检测低水平的脱落。在没有直肠性STI的情况下，在此提供了初步数据 与成人HIV阴性MSM的应用18-45岁，显示出独特的先天和适应性促炎 对直肠粘膜中无避孕套肛门性交（CRAI）的免疫反应，多样性 直肠粘膜微生物群的组成在参与CRAI与男性的成年MSM之间有所不同 谁不从事肛交（AI），而MSM参与Crai为家人丰富 Prevotellaceae。在此应用中，我们建议扩展我们的直肠粘膜研究MSM以检查 细菌性STI对直肠粘膜常见的细胞种群（AIM1）和微生物组（AIM2）的影响。在 AIM 3，我们将研究STI治疗后炎症的分辨率及其对离体HIV感染的影响 直肠粘膜。我们将以高度的高度转化粘膜免疫学计划为基础 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。更好地理解直肠中对STI的宿主反应 将对生物医学HIV和细菌性STI预防机制的设计有用，包括有效 疫苗。