Epidemiologic studies demonstrate that DMPA may increase the risk of HIV acquisition and transmission. Additionally, Depo-Provera has been shown to attenuate the vaccine efficacy to protect rhesus macaques against SIV infection. The impact of hormonal contraceptive use on HIV acquisition and transmission has profound implications for polices on family planning, particularly in countries with high rates of HIV transmission. While progesterone clearly enhances vaginal transmission of SIV/SHIV in rhesus macaques, the effect of progestin-based hormone on HIV acquisition/transmission in women remains unresolved. We hypothesize that injectable DMPA alters immune responses and cervicovaginal and colonic microbiomes, which may lead to increased HIV acquisition and transmission.
The aims of this proposal are designed to (1) determine the impact of Depo-Provera on the systemic and mucosal immune systems and on cervicovaginal and colonic microbiomes in a longitudinal study, and (2) to elucidate the immune mechanisms of MPA-mediated modulation of HIV infection/transmission in vitro, ex vivo and in cervical explant models. Blood, cervicovaginal specimens and stool samples will be collected at baseline (both follicular and luteal phases) and after 4, and 8 weeks of DMPA injection. The immunological profiles of CD4+ T cells and their susceptibility to HIV will be characterized. We will determine the temporal impact of DMPA on cervicovaginal and colonic microbiome. Global alteration and changes in specific taxa will be correlated with immunological changes. The results of our studies will provide a better understanding of how DMPA modulates immunologic responses and microbiomes, thereby informing the design of effective HIV prevention strategies.

Public Health Relevance

The goal of this project is to understand the mechanism by which Depo-Provera enhances HIV acquisition and transmission in women. We will investigate alteration of immune responses and microbiome in a longitudinal study and dissect the underlying mechanism of an increase in HIV susceptibility and transmission by Depo-Provera. The results of our studies will offer important insights into development of effective strategies fr HIV prevention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI110372-01
Application #
8593906
Study Section
Special Emphasis Panel (ZHD1-DSR-A (55))
Program Officer
Porter, Kristen A
Project Start
2013-08-09
Project End
2018-07-31
Budget Start
2013-08-09
Budget End
2014-07-31
Support Year
1
Fiscal Year
2013
Total Cost
$522,582
Indirect Cost
$160,917
Name
Rutgers University
Department
Type
DUNS #
078795851
City
Newark
State
NJ
Country
United States
Zip Code
07103
Baghdadi, Jonathan; Chaudhary, Noami; Pei, Zhiheng et al. (2014) Microbiome, innate immunity, and esophageal adenocarcinoma. Clin Lab Med 34:721-32
Salas, January T; Chang, Theresa L (2014) Microbiome in human immunodeficiency virus infection. Clin Lab Med 34:733-45
Tasker, Carley; Ding, Jian; Schmolke, Mirco et al. (2014) 17?-estradiol protects primary macrophages against HIV infection through induction of interferon-alpha. Viral Immunol 27:140-50