Impact of progestin contraception on risk of HIV acquisition and transmission

产品说明：该提案概述了一个5年的职业发展计划和研究战略，使我能够加强我在OB-GYN/计划生育方面的背景，在生殖传染病转化研究方面具有额外的技能和熟练程度，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机制。 职业发展计划：在完成了为期2年的计划生育奖学金，并接受了深入的避孕培训和公共卫生硕士学位后，我具备了临床研究方法的基本基础。在此基础上，目前的建议将与生殖健康有关的基础医学与高级课程结合起来。强调三个主要领域：1）多学科指导; 2）在病毒学，免疫学和先进的临床研究方法的教学培训;和3）在相关的基础科学技术的动手实验室培训。导师团队包括Igho Ofotokun博士，他是NIH资助的研究人员，在艾滋病毒感染的妇女健康研究方面拥有丰富的经验，Denise Jamieson博士是埃默里大学的兼职教授，也是疾病控制中心（CDC）生殖健康部妇女健康和生育分支主任。我的长期目标是成为生殖传染病领域的独立临床科学家，重点是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性环境，以及合作关系 能促进我的职业发展 研究计划：我建议围绕概念验证前瞻性队列设计发展我的转化研究经验。针对HIV阴性女性，3个拟议目标将评估长效醋酸甲羟孕酮（DMPA）、依托孕烯植入剂（Eng-Implant）和左炔诺孕酮宫内节育器（Lng-IUD）暴露于1）女性生殖器粘膜内的HIV靶向免疫细胞; 2）女性生殖器粘膜内T细胞活化和运输的标志物;和3）在女性生殖器粘膜内分泌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HIV靶向免疫细胞和女性生殖器粘膜内功能的改变是与外源性激素的药理学剂量相关的相对较高的HIV风险的基础，因为仅孕激素避孕药的预期粘膜免疫变化在很大程度上是通过雌激素抑制介导的，与DMPA相比，Eng-Implant和Lng-IUD（具有较温和的抗雌激素作用）的影响预期显著较不显著。这项研究的结果可能对全球妇女提供计划生育服务具有重要的临床意义。

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.