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.
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.
|Tasker, Carley; Subbian, Selvakumar; Gao, Pan et al. (2016) IFN-Îµ protects primary macrophages against HIV infection. JCI Insight 1:e88255|
|Yang, Liying; Poles, Michael A; Fisch, Gene S et al. (2016) HIV-induced immunosuppression is associated with colonization of the proximal gut by environmental bacteria. AIDS 30:19-29|
|Shin, Hakdong; Pei, Zhiheng; Martinez 2nd, Keith A et al. (2016) Erratum to: The first microbial environment of infants born by C-section: the operating room microbes. Microbiome 4:4|
|Guma, Sergei; Maglantay, Remegio; Lau, Ryan et al. (2016) Papillary urothelial carcinoma with squamous differentiation in association with human papilloma virus: case report and literature review. Am J Clin Exp Urol 4:12-6|
|Ren, Wuze; Ma, Yingfei; Yang, Liying et al. (2015) Fast disease progression in simian HIV-infected female macaque is accompanied by a robust local inflammatory innate immune and microbial response. AIDS 29:F1-8|
|Shin, Hakdong; Pei, Zhiheng; Martinez 2nd, Keith A et al. (2015) The first microbial environment of infants born by C-section: the operating room microbes. Microbiome 3:59|
|Ding, Jian; Tasker, Carley; Lespinasse, Pierre et al. (2015) Integrin Î±4Î²7 Expression Increases HIV Susceptibility in Activated Cervical CD4+ T Cells by an HIV Attachment-Independent Mechanism. J Acquir Immune Defic Syndr 69:509-18|
|Pincus, Matthew R; Pei, Zhiheng (2014) Beyond infectious disease: welcome to the era of population microbiology. Clin Lab Med 34:xi-xiii|
|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) 17Î²-estradiol protects primary macrophages against HIV infection through induction of interferon-alpha. Viral Immunol 27:140-50|
Showing the most recent 10 out of 11 publications