Syndemics, the microbiome, and mucosal inflammation involved in HIV acquisition

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Project Summary/Abstract Background. A Syndemic occurs when harmful social contexts (e.g., poverty and discrimination) fuel interacting biological and psychological health conditions that increase risk for diseases such as HIV. Syndemics of poor mental health, substance use, and trauma have shown relationships with sexual risk and HIV seroconversion among women and sexual minority men (i.e., gay, bisexual, and other men who have sex with men). However, there is a need for additional research on common biological pathways through which Syndemics may impact the immune system to amplify risk of HIV acquisition in high priority populations. The most likely route of HIV infection is through the rectal or cervicovaginal mucosa. Dysbiosis (non-optimal microbiome composition) and local inflammation are associated with decreased mucosal immunological capabilities, increasing the risk of HIV acquisition. Mental health, substance use, and risk behaviors have shown separate relationships to dysbiosis and inflammation. However, no research has modeled these factors together as a Syndemic and explored the Syndemic correlates of rectal or cervicovaginal dysbiosis and characteristics of the vaginal/rectal environments associated with decreased mucosal immunity. Methods. This F32 will involve two approaches: (1) conduct a sub-study that will add psychosocial Syndemic measures to an ongoing R01 (5R01AI138718-02; PI: Alcaide) investigating predictors of bacterial vaginosis among women to examine the relationships among Syndemic factors (e.g., mental health, substance use, trauma) and vaginal dysbiosis and (2) leverage existing 16S rRNA sequencing data from a recently completed study of 92 HIV- negative sexual minority men in South Florida recruited in STI clinics to examine the relationship between Syndemic conditions and rectal dysbiosis (AIDS Healthcare Foundation; PI: Carrico). Through both studies, essential knowledge will be gained on the relevance of a dysbiotic microbiome as a common pathway explaining how Syndemic processes could amplify HIV risk in priority populations. Training Plan. Through hands-on training, didactics, and meetings with a multidisciplinary mentorship team (Carrico, Klatt, Alcaide, and Safren), the applicant will gain training on psychoneuroimmunology in HIV prevention, with a focus on the microbiome and mucosal immunology, and obtain exposure to sequencing-based bioinformatics analysis to bridge the fields of clinical psychology and mucosal immunology. This F32 fellowship application will lay the groundwork for a K23 proposal to develop and test bio-behavioral interventions targeting Syndemic conditions to improve mental health, address dysbiosis of the microbiome, and improve mucosal immune functioning relevant to HIV acquisition in high priority populations. Implications. Findings from this F32 research and training plan represent an important first step towards an independent research program focusing on biological mechanisms connecting Syndemic conditions and mucosal immune functioning, with the aim of decreasing HIV-related health disparities experienced by marginalized populations.