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.

Public Health Relevance

Hormonal contraception is a central component in the prevention of unintended pregnancy, and is widely used among reproductive aged women regardless of HIV status. However, recent epidemiologic reports have suggested that certain hormonal contraceptives, specifically DMPA, may increase the risk of HIV infection. This proposal will explore potential mechanisms associated with this purported risk, and assess the relative impact of 3 progestin-only contraceptives (DMPA, Eng-Implant and Lng-IUD) on surrogates of HIV susceptibility within the female genital tract.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HD078153-04
Application #
9245716
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Russo, Denise
Project Start
2014-04-10
Project End
2019-03-31
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
4
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Emory University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Gausi, Blessings; Chagomerana, Maganizo B; Tang, Jennifer H et al. (2018) Human Immunodeficiency Virus Serodiscordance and Dual Contraceptive Method Use Among Human Immunodeficiency Virus-infected Men and Women in Lilongwe, Malawi. Sex Transm Dis 45:747-753
Haddad, Lisa B; Tang, Jennifer H; Krashin, Jamie et al. (2018) Factors associated with condom use among men and women living with HIV in Lilongwe, Malawi: a cross-sectional study. BMJ Sex Reprod Health 44:1-12
Brown, Jennifer L; Haddad, Lisa B; Gause, Nicole K et al. (2018) Examining the contraceptive decisions of young, HIV-infected women: A qualitative study. Women Health :1-13
Gausi, Blessings; Chagomerana, Maganizo B; Tang, Jennifer H et al. (2018) HIV Sero-discordance and dual contraceptive method use among HIV-infected men and women in Lilongwe, Malawi. Sex Transm Dis :
Jamieson, Denise J; Haddad, Lisa B (2018) What Obstetrician-Gynecologists Should Know About Population Health. Obstet Gynecol 131:1145-1152
Nwaohiri, Anuli N; Tang, Jennifer H; Stanczyk, Frank et al. (2018) Discordance between self-reported contraceptive use and detection of exogenous hormones among Malawian women enrolling in a randomized clinical trial. Contraception 97:354-356
Haddad, Lisa B; Wall, Kristin M; Kilembe, William et al. (2018) Bacterial vaginosis modifies the association between hormonal contraception and HIV acquisition. AIDS 32:595-604
Haddad, Lisa B; Horton, John; Ribner, Bruce S et al. (2018) Ebola Infection in Pregnancy: A Global Perspective and Lessons Learned. Clin Obstet Gynecol 61:186-196
Hynes, Jenna S; Sales, Jessica M; Sheth, Anandi N et al. (2018) Interest in multipurpose prevention technologies to prevent HIV/STIs and unintended pregnancy among young women in the United States. Contraception 97:277-284
Mann, Taylor Z; Haddad, Lisa B; Williams, Tonya R et al. (2018) Breast milk transmission of flaviviruses in the context of Zika virus: A systematic review. Paediatr Perinat Epidemiol 32:358-368

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