Impact of progestin contraception on risk of HIV acquisition and transmission

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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.