Hormones, Immunity and HIV Risk

激素、免疫和艾滋病毒风险

• 批准号: 9479239
• 负责人: KATHERINE E BUNGE
• 金额: $ 43.83万
• 依托单位: MAGEE-WOMEN'S RES INST AND FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-01 至 2021-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9479239
• 关键词: 19 year old; Address; Adolescent; Adult; Affect; Age; Ambulatory Care Facilities; Behavior; Biological; Biological Factors; Biopsy; CCR5 gene; CCR6 gene; CD14 gene; Cells; Cervical; Chara; Clinical; Coercion; Communities; Contraceptive Agents; Contraceptive Usage; Contraceptive methods; Cross-Sectional Studies; Data; Dendritic Cells; Enrollment; Epidemic; Epidemiology; Epithelial; Epithelium; Etonogestrel; Evaluation; Exposure to; Female; Female Adolescents; Flow Cytometry; Gender; Genital system; Goals; HIV; HIV Infections; HIV risk; Health; Health Services Accessibility; Heptanoates; Hormonal; Hormones; Hospitals; ITGAX gene; Immune; Immunity; Implant; In Vitro; Incidence; Income; Inequality; Infection; Inflammation; Injections; Intrauterine Devices; Knowledge; Lactobacillus; Levonorgestrel; Link; Liquid substance; Measures; Mediator of activation protein; Medroxyprogesterone 17-Acetate; Methods; Mucosal Immunity; Mucous Membrane; Norethindrone; Persons; Population; Predisposition; Pregnancy; Pregnancy Rate; Progesterone; Progestins; Proteins; Proteome; Proteomics; Reproducibility; Risk; Sexual Partners; Sexually Transmitted Diseases; Skin; Specimen Handling; System; T-Lymphocyte; Testing; Tissues; Unwanted pregnancy; Upper arm; Uterus; Vagina; Virus; Woman; Work; aged; cervicovaginal; condoms; functional outcomes; girls; hormonal contraception; improved; macrophage; microbiota; next generation; pathogen; pregnant; recruit; reproductive tract; reversible contraceptive; sex; sexual debut; sexual relationship; success; vaginal fluid; viral RNA; young woman

ABSTRACT Our over arching goal of this application is to determine if exogenous progestins used in long acting reversible contraceptives (LARCs) will enhance adolescent risk for mucosal HIV acquisition. In the U.S., persons aged 13-24 years accounted for 26% of all new HIV infections. The HIV epidemic in adolescent girls reflects the strong combined impact of gender and income inequality, early sexual debut, age disparate sexual relationships, psychosexual maturation, sociocultural context, and heightened biological vulnerability. Exogenous progestins, expecially medroxyprogesterone acetate (MPA), have been epidemiologically linked to greater HIV acquisition. Gaps remain in our understanding of biological factors that might be associated with increased risk of HIV acqusition in adolescent girls and how exogenous progestins will influence this risk. LARCs use is encouraged for all women desiring to not become pregnant as they release progestins over 3 to 5 years. Typical LARCs include etonogestrel implants (ENG-I) or levonorgestrel-intrauterine system (LNG- IUS). Our preliminary data shows cervical tissue collected from women using MPA and LNG-IUS for contraception replicates HIV 2- to 3.5-fold higher than cervical tissue from non-contracepting women. Therefore, our aims center on potential genital tract differences non-contracepting and contracepting (ENG-I and LNG-IUS) 120 adolescents (18 to 19 years old) and correlate our findings to non-contracepting and contracepting 90 adult women (≥25 years old). First, differences in the capcity of cerivcal tissue to replicate HIV will be assess between the groups and associated with resident cell populations. Secondly, the vaginal fluid and epithelium, which provide the first line of defense against pathogens, including HIV, will be systematically studied. Vaginal fluid will be characterized for the microflora and the soluble mucosal proteins using an unbiased proteomic approach. These results will be correlated to functional activity of the luminal fluid as measured by in vitro anti-HIV activity. Our premise is that non-contracepting adolescent women will demonstrate higher levels of mediators and activated immune cells that are associated with increased HIV infection compared to more mature women. However, contracepting adolescent and adult women will have comparable levels of the mediators, activated immune cells, and capacity of tissue to replicate HIV. A key challenge will be the recruitment of adolescent girls. Our advantage is that adolescents frequent the outpatient clinic at Magee Womens Hospital and our clinical team has worked with adolescents in other studies, which overcomes many of the recruitment challenges. We have close working relationships among the groups represented in this application and have optimized specimen handling/processing/testing which is key for reproducibility in our work. This application will uniquely associate quantified analyses with functional outcomes and begin to address if exogenous progestins impose additional risk of HIV acquisition to young women.

抽象的 我们该应用程序的过度拱门目标是确定长期可逆的外源孕激素是否使用 避孕药（LARCS）将增加粘膜艾滋病毒获取的青少年风险。在美国，年龄的人 13 - 24年占所有新艾滋病毒感染的26％。青春期女孩的艾滋病毒流行反映了 性别和收入不平等，早期性行为，年龄分歧的强烈综合影响 人际关系，心理性成熟，社会文化背景和增强的生物脆弱性。 外源孕激素，乙酸二甲酸酯（MPA）已在流行病学上与 艾滋病毒收购更大。我们对可能与的生物因素有关的差距仍然存在 青春期女孩中艾滋病毒获取的风险增加，以及外源孕激素将如何影响这种风险。 鼓励所有希望不怀孕的女性在3至 5年。典型的LARC包括EtonogeTretel（Eng-I）或左旋癌症系统（LNG-） ius）。我们的初步数据显示，使用MPA和LNG-IUS从女性那里收集宫颈组织 避孕措施复制了来自非注射妇女的宫颈组织2至3.5倍的HIV。 因此，我们的目的是潜在生殖道差异的中心，非构造和避孕（ENG-I） 和lng-ius）120名青少年（18至19岁），并将我们的发现与非控制和 避孕90名成年妇女（≥25岁）。首先，cerivcal组织的能力差异复制 两组之间将评估HIV，并与居民细胞种群相关。其次，阴道 流体和上皮提供了针对病原体（包括艾滋病毒）的第一道防线 系统地研究。阴道流体将以微生物和固体粘膜蛋白为特征 使用公正的蛋白质组学方法。这些结果将与腔流体的功能活性相关 通过体外抗HIV活性测量。我们的前提是，非注释的青少年妇女将 证明较高水平的介体和激活的免疫细胞与HI​​V增加有关 与更成熟的女性相比，感染。但是，避孕青少年和成年女性将拥有 可比水平的介体，激活的免疫球和组织复制HIV的能力。钥匙 挑战将是青春期女孩的招募。我们的优势是青少年经常门诊 Magee Womens Hospital和我们的临床团队的诊所与其他研究中的青少年合作， 克服了许多招聘挑战。我们之间有着密切的工作关系 在此应用程序中表示，并优化了标本处理/处理/测试，这是 我们工作中的可重复性。该应用程序将唯一将量化分析与功能结果相关联 并开始解决外源孕激素是否对年轻妇女施加艾滋病毒的额外风险。