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 #
1K23HD078153-01A1
Application #
8732380
Study Section
Special Emphasis Panel ()
Program Officer
Russo, Denise
Project Start
2014-04-10
Project End
2019-03-31
Budget Start
2014-04-10
Budget End
2015-03-31
Support Year
1
Fiscal Year
2014
Total Cost
$127,035
Indirect Cost
$9,410
Name
Emory University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Hynes, Jenna S; Sales, Jessica M; Sheth, Anandi N et al. (2017) Interest in multipurpose prevention technologies to prevent HIV/STIs and unintended pregnancy among young women in the United States. Contraception :
Haddad, Lisa B; Monsour, Michael; Tepper, Naomi K et al. (2017) Trends in contraceptive use according to HIV status among privately insured women in the United States. Am J Obstet Gynecol 217:676.e1-676.e11
Haddad, Lisa B; Wall, Kristin M; Mehta, C Christina et al. (2017) Trends of and factors associated with live-birth and abortion rates among HIV-positive and HIV-negative women. Am J Obstet Gynecol 216:71.e1-71.e16
Kourtis, Athena P; Haddad, Lisa; Tang, Jennifer et al. (2017) A randomized clinical trial on the effects of progestin contraception in the genital tract of HIV-infected and uninfected women in Lilongwe, Malawi: Addressing evolving research priorities. Contemp Clin Trials 52:27-34
Hatfield-Timajchy, Kendra; Brown, Jennifer L; Haddad, Lisa B et al. (2016) Parenting Among Adolescents and Young Adults with Human Immunodeficiency Virus Infection in the United States: Challenges, Unmet Needs, and Opportunities. AIDS Patient Care STDS 30:315-23
Wall, Kristin M; Kilembe, William; Haddad, Lisa et al. (2016) Hormonal Contraception, Pregnancy, Breastfeeding, and Risk of HIV Disease Progression Among Zambian Women. J Acquir Immune Defic Syndr 71:345-52
Swaims-Kohlmeier, Alison; Haaland, Richard E; Haddad, Lisa B et al. (2016) Progesterone Levels Associate with a Novel Population of CCR5+CD38+ CD4 T Cells Resident in the Genital Mucosa with Lymphoid Trafficking Potential. J Immunol 197:368-76
Rimawi, Bassam H; Smith, Somer L; Badell, Martina L et al. (2016) HIV and reproductive healthcare in pregnant and postpartum HIV-infected women: adapting successful strategies. Future Virol 11:577-581
Wall, Kristin M; Kilembe, William; Vwalika, Bellington et al. (2016) Hormonal Contraceptive Use Among HIV-Positive Women and HIV Transmission Risk to Male Partners, Zambia, 1994-2012. J Infect Dis 214:1063-71
Rimawi, Bassam H; Haddad, Lisa; Badell, Martina L et al. (2016) Management of HIV Infection during Pregnancy in the United States: Updated Evidence-Based Recommendations and Future Potential Practices. Infect Dis Obstet Gynecol 2016:7594306

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