The objective of this proposal is to study effects of a contraceptive vaginal ring (CVR) on vaginal bacteria in women, and relate these changes to key measures of soluble mucosal host immune defense. We will build on limited data suggesting a favorable effect of CVR on vaginal bacteria, which comprise a critical first line of defense against infection with HIV and other sexually transmitted infections (STI).
In Aim 1, we will determine the effect of the CVR on vaginal bacteria. The goal is to study whether sustained vaginal delivery of estrogen promotes healthy vaginal populations of desirable LB, and thus reduces risk of incident and persistent BV. Women with or at risk for BV will be enrolled and prior to CVR initiation will be assessed with bacterium-specific quantitative PCR (qPCR) assays for key lactobacilli and BV-associated bacteria (BVAB). After they initiate CVR, they will return monthly over 4 subsequent months for assessment. qPCR results will be used to determine how concentrations of vaginal bacteria change in presence of absence of CVR. We hypothesize that: CVR use will be associated with favorable vaginal change assessed by BVAB qPCR.
In Aim 2, we will measure key parameters of the soluble mucosal host immune response and endocervical immune cell populations with CVR use, including restoration of protective immune mediators that are decreased in the setting of BV such as SLPI, defensins, and lactoferrrin, and reduction in pro- inflammatory cytokines and the number of activated T-cells in the endocervix. Endocervical swabs, cytobrushes and cervicovaginal lavage will be collected at each visit and concentrations of mediators measured.
In Aim 3, we will evaluate incidence of lower genital tract infection, primarily BV, before and after establishment of the CVR. We hypothesize that CVR use will promote a desirable Lactobacillus-predominant, non-inflammatory vaginal environment with reduced frequency and quantity of BV.

Public Health Relevance

Limited data suggesting a favorable effect of the contraceptive vaginal ring (CVR) on vaginal bacteria, which comprise a critical first line of defense against sexually transmitted infections (STI). The goal is to study whether sustained vaginal delivery of estrogen promotes healthy vaginal populations of desirable vaginal bacteria (specific species of lactobacilli), and thus reduces risk of incident and persistent bacterial vaginosis (BV). Bacterial vaginosis (BV) is a common cause of vaginitis and increases women's risk of pelvic inflammatory disease, adverse pregnancy outcomes, and risk of HIV acquisition. The etiology of BV is unclear, and BV frequently recurs. We will use our molecular tools to study whether CVR use will promote a healthy vaginal environment, thereby contributing to a reduction of BV risk.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1)
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University of Washington
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Khosropour, Christine M; Dombrowski, Julia C (2018) A Web of Complexity: Untangling the Routes of Rectal Chlamydia Acquisition. Sex Transm Dis 45:511-513
Fink, Susan L; Vojtech, Lucia; Wagoner, Jessica et al. (2018) The Antiviral Drug Arbidol Inhibits Zika Virus. Sci Rep 8:8989
Reeves, Daniel B; Duke, Elizabeth R; Wagner, Thor A et al. (2018) A majority of HIV persistence during antiretroviral therapy is due to infected cell proliferation. Nat Commun 9:4811
Khosropour, Christine M; Bell, Teal R; Hughes, James P et al. (2018) A Population-Based Study to Compare Treatment Outcomes Among Women With Urogenital Chlamydial Infection in Washington State, 1992 to 2015. Sex Transm Dis 45:319-324
Balle, Christina; Lennard, Katie; Dabee, Smritee et al. (2018) Endocervical and vaginal microbiota in South African adolescents with asymptomatic Chlamydia trachomatis infection. Sci Rep 8:11109
Gasper, Melanie A; Hesseling, Anneke C; Mohar, Isaac et al. (2017) BCG vaccination induces HIV target cell activation in HIV-exposed infants in a randomized trial. JCI Insight 2:e91963
Manhart, Lisa E (2017) Mycoplasma genitalium on the Loose: Time to Sound the Alarm. Sex Transm Dis 44:463-465
Herbst-Kralovetz, Melissa M; Pyles, Richard B; Ratner, Adam J et al. (2016) New Systems for Studying Intercellular Interactions in Bacterial Vaginosis. J Infect Dis 214 Suppl 1:S6-S13
Gasper, Melanie A; Biswas, Shameek P; Fisher, Bridget S et al. (2016) Nonpathogenic SIV and Pathogenic HIV Infections Associate with Disparate Innate Cytokine Signatures in Response to Mycobacterium bovis BCG. PLoS One 11:e0158149
Manhart, Lisa E; Khosropour, Christine M (2015) Launching a new era for behavioural surveillance. Sex Transm Infect 91:152-3

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