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.

项目总结