Impact of progestin contraception on risk of HIV acquisition and transmission

描述：这项建议概述了一个5年的职业发展计划和研究战略，使我能够通过更多的技能和精通生殖传染病的翻译研究来加强我在妇产科/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：我完成了为期两年的计划生育研究，接受了深入的避孕培训，并获得了公共卫生硕士学位，具备了临床研究方法论的基本基础。在此基础上，目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。重点强调三个主要领域：1)多学科指导；2)病毒学、免疫学和高级临床研究方法学的教学培训；3)相关基础科学技术的实验室实践培训。导师团队包括NIH资助的研究员Igho Ofotokun博士和Denise Jamieson博士，前者是NIH资助的研究员，在艾滋病毒感染的妇女健康研究方面拥有丰富的经验，后者是Emory的兼职教授，也是疾病控制中心(CDC)生殖健康司的妇女健康和生育科主任。我的长期目标是成为生殖传染病领域的一名独立临床科学家，专注于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翻译科学研究所提供的支持环境，以及合作关系 在疾控中心工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发展我的翻译研究经验。这3个拟议目标将以HIV阴性女性为重点，评估储备醋酸甲羟孕酮(DMPA)、依托孕酮植入剂(Eng-Impot)和左旋诺孕酮宫内节育器(LNG-IUD)暴露对1)女性生殖器粘膜内的HIV靶向免疫细胞；2)女性生殖器黏膜内T细胞激活和运输的标志物；以及3)女性生殖器黏膜内分泌的细胞因子和趋化因子的影响。一组预期招募的艾滋病毒阴性妇女将允许检验最重要的假设，即女性生殖器粘膜内艾滋病毒靶免疫细胞和功能的变化是与外源性性激素的药理剂量相关的相对较高的艾滋病毒风险的基础，因为仅使用孕激素避孕药预期的粘膜免疫变化在很大程度上是通过雌激素抑制来调节的，Eng-Impot和LNG-IUD(具有较温和的抗雌激素作用)的影响预计将明显低于DMPA。拟议研究的结果可能对向全世界妇女提供计划生育服务产生重大的临床影响。

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.