Impact of progestin contraception on risk of HIV acquisition and transmission

孕激素避孕对艾滋病毒感染和传播风险的影响

• 批准号: 8732380
• 负责人: Lisa Blake Haddad
• 金额: $ 12.7万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-10 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8732380
• 关键词: Acquired Immunodeficiency Syndrome; Anti-Inflammatory Agents; Anti-inflammatory; Area; Basic Science; CD4 Positive T Lymphocytes; Cell physiology; Cells; Centers for Disease Control and Prevention (U.S.); Clinical; Clinical Research; Communicable Diseases; Contraceptive Agents; Contraceptive Usage; Contraceptive methods; Data; Development Plans; Dose; Drug Kinetics; Environment; Epidemiology; Epithelial; Estrogen Antagonists; Estrogens; Etonogestrel; Evaluation; Exposure to; Family Planning; Fellowship; Female; Fertility; Fostering; Foundations; Frequencies; Funding; Genital system; Goals; Gonadal Steroid Hormones; HIV; HIV Infections; HIV risk; High Prevalence; High Risk Woman; Hormonal; Immune; Immune Targeting; Immune response; Immunity; Immunologic Markers; Immunologics; Immunology; Implant; Institutes; Intrauterine Devices; Laboratories; Levonorgestrel; Light; Literature; Master of Public Health; Mediating; Medical; Medroxyprogesterone 17-Acetate; Mentors; Mentorship; Mirena; Mucous Membrane; Organon brand of 3-keto-desogestrel; Outcome; Population; Predisposition; Prevention; Progesterone; Progestins; Prospective Studies; Public Health; Recruitment Activity; Relative (related person); Reporting; Reproductive Health; Reproductive Immunology; Research; Research Methodology; Research Personnel; Risk; SIV; Safety; Science; Scientist; Site; Synthetic Progestogens; T-Cell Activation; T-Lymphocyte; Techniques; Training; Translational Research; United States National Institutes of Health; Universities; Vagina; Woman; Women' s Health; Work; aged; career development; chemokine; cohort; cytokine; design; experience; high risk; hormonal contraception; immune function; multidisciplinary; nonhuman primate; pathogen; professor; prospective; public health relevance; reproductive; research and development; sexually active; skills; trafficking; transmission process; unintended pregnancy; virology

DESCRIPTION: This proposal outlines a 5-year career development plan and research strategy that enables me to bolster my background in OB-GYN/family planning with additional skills and proficiency in translational research in reproductive infectious diseases and to conduct a proof of concept study to explore the mechanisms underlying the risk of HIV acquisition associated with hormonal contraception. Career Development Plan: Having completed a 2-year fellowship in family planning with in-depth training on contraception and a Master of Public Health degree, I possess a basic foundation in clinical research methodology. Expanding on this foundation, the current proposal integrates aspects of basic medical sciences relevant to reproductive health with advanced coursework. Three major areas are emphasized: 1) Multidisciplinary mentorship; 2) Didactic training in virology, immunology, and advanced clinical research methodology; and 3) Hands-on laboratory training in relevant basic science techniques. The team of mentors includes Dr. Igho Ofotokun, an NIH-funded investigator with vast experience in women's health research in HIV infection and Dr. Denise Jamieson, an adjunct professor at Emory and Chief of the Women's Health and Fertility Branch, Division of Reproductive Health at the Centers for Disease Control (CDC). My long-term goal is to become an independent clinician scientist in the field of reproductive infectious diseases with a focus on safe family planning in high-risk populations. The supportive environment offered by Emory University, the Center for AIDS Research, and the Atlanta Clinical Translational Science Institute, in addition to the collaborative relationship with CDC will foster my career development. Research Plan: I propose to develop my translational research experience around a proof of concept prospective cohort design. Focusing on HIV negative women, the 3 proposed aims will evaluate the effect of depot medroxyprogesterone acetate (DMPA), Etonogestrel impant (Eng-Implant) and Levonorgestrel intrauterine device (Lng-IUD) exposure on 1) HIV target immune cells within the female genital mucosa; 2) markers of T-cell activation and trafficking within the female genital mucosa; and 3) secreted cytokines and chemokines within the female genital mucosa. A prospectively recruited cohort of HIV negative women will allow the examination of the overarching hypothesis that alterations in HIV target immune cells and function within the female genital mucosa underlie the relatively higher HIV risk associated with the pharmacologic doses of exogenous sex hormones, Because the anticipated mucosal immune changes with progestin-only contraceptives are to a large extent mediated via estrogen suppression, the impact of Eng-Implant and Lng- IUD (with milder anti-estrogen effect) is expected to be significantly less pronounced compared with that of DMPA. The outcomes of the proposed study could have significant clinical implications for the provision of family planning services fo women worldwide.

描述：该提案概述了一个 5 年职业发展计划和研究策略，使我能够通过生殖传染病转化研究的额外技能和熟练程度来增强我在妇产科/计划生育方面的背景，并进行概念验证研究，以探索与激素避孕相关的艾滋病毒感染风险的潜在机制。 职业发展计划： 完成了为期 2 年的计划生育研究金，并接受了避孕方面的深入培训并获得了公共卫生硕士学位，我在临床研究方法方面拥有了基础。在此基础上进行扩展，当前的提案将与生殖健康相关的基础医学方面与高级课程相结合。强调三个主要领域：1）多学科指导； 2) 病毒学、免疫学和先进临床研究方法的教学培训； 3) 相关基础科学技术的实践实验室培训。导师团队包括 Igho Ofotokun 博士（美国国立卫生研究院资助的研究员，在艾滋病毒感染的女性健康研究方面拥有丰富经验）和 Denise Jamieson 博士（埃默里大学兼职教授、美国疾病控制中心 (CDC) 生殖健康司妇女健康和生育处处长）。我的长期目标是成为生殖传染病领域的独立临床科学家，重点关注高危人群的安全计划生育。埃默里大学、艾滋病研究中心和亚特兰大临床转化科学研究所提供的支持环境以及合作关系 与 CDC 合作将促进我的职业发展。 研究计划：我建议围绕概念验证前瞻性队列设计来发展我的转化研究经验。针对 HIV 阴性女性，提出的 3 个目标将评估长效醋酸甲羟孕酮 (DMPA)、依托孕烯埋植剂 (Eng-Implant) 和左炔诺孕酮宫内节育器 (Lng-IUD) 暴露对以下方面的影响： 1) 女性生殖器粘膜内的 HIV 目标免疫细胞； 2) 女性生殖器粘膜内 T 细胞激活和运输的标记物； 3) 女性生殖器粘膜内分泌的细胞因子和趋化因子。前瞻性招募的 HIV 阴性女性队列将允许检查总体假设，即女性生殖器粘膜内 HIV 目标免疫细胞和功能的改变是与外源性激素药理剂量相关的相对较高 HIV 风险的基础。 与 DMPA 相比，Lng-IUD（具有较温和的抗雌激素作用）预计明显不那么明显。拟议研究的结果可能对为全世界妇女提供计划生育服务产生重大临床影响。