Bacterial vaginosis (BV), which is characterized by a dysbiotic vaginal microbiota low in Lactobacillus species, affects nearly 30% of U.S. women; the majority (55%) are asymptomatic (aBV). Guidelines currently recommend testing and treatment only for symptomatic BV (sBV). BV (a composite variable with aBV and symptomatic BV [sBV]) has been associated with an increased risk of sexually transmitted infections (STIs) and HIV acquisition. Although studies to distinguish the differential risk of incident STI or HIV between women with aBV and sBV have not been published, preliminary data from our group suggests that aBV is strongly associated with incident STI and a published pilot study of BV suppressive therapy in women with aBV indicated a decrease in chlamydia cases. To date, enthusiasm for research on or clinical treatment of aBV has been limited, primarily by lack of data on aBV risks and perceptions of low efficacy of currently available BV treatments. However, while BV treatment is challenging, approximately 50% of women with sBV taking currently available therapies do achieve lasting cure. Moreover, novel, more effective therapies for BV are on the horizon: a recent high-profile randomized trial of Lactin V, a L. crispatus intravaginal live biotherapeutic product, showed reduced BV recurrence13. As new, better treatments for sBV become available, it is critical to determine whether women with aBV should also be treated, in order to prevent sequelae such as STI or HIV acquisition. If the vaginal microenvironment is shown to be identical in women with sBV and aBV, this will be an important initial step demonstrating that aBV is a condition that should not be ignored, and will galvanize further studies to define aBV, STI and HIV risk, and advance treatment. In a large epidemiologic study of over 300 women, our specific aims are to assess whether women with aBV and sBV differ in two broad areas (1) biobehavioral factors and (2) the vaginal microenvironment, including factors associated with HIV and STI acquisition risk (vaginal microbiota, key metabolites and soluble mediators of inflammation). This is a secondary analysis leveraging existing data from a previously funded study (NIAID R01-AI116799, PI: Brotman) for which 16S rRNA gene amplicon, metabolomic, and immunologic profiles have already been generated from cervicovaginal lavage samples collected in the NIH's Longitudinal Study of Vaginal Flora. Information gained through this proposed study will provide foundational data to better define aBV, and to determine whether future studies to define the risk of HIV and STI acquisition associated with aBV, or studies of aBV treatment as a method to prevent HIV and STIs are needed. This resubmission application is in response to a program announcement (PAR-20-291) which is designed for Exploratory and Developmental Research Grant Program for NIAID K-award Recipients. It will provide career development for the PI to transition to research independen...