Psycho-neuro-immune Mechanisms Linking Stigma and Discrimination to Carotid Plaque Formation in Persons living with HIV

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Abstract: Persons living with HIV experience constant stigma and discrimination. The project objective is to model the impact of the psychosocial experiences of stigma/discrimination on the complex interactions between multiple systems (neural, immune, and autonomic) that give rise to atherosclerotic processes in the context of treated chronic HIV-infection. This project assembles a multi-disciplinary team that will decipher the complexity of these interactions within a cohort of 150 racially, ethnically, and sexually diverse persons living with HIV (PWH) between the ages of 35-55 years that have stable anti-retroviral regimens and detectable viral loads without history of heart failure. The study aims to test two separate psycho-neuro-immune mediation models for experiences of social rejection and discrimination on carotid plaque formation measured through high resolution ultrasound. In the first model, using an interactive functional magnetic resonance imaging (fMRI) paradigm, change from pre- to post-task peripheral blood monocyte activation and expression of IL-6 will be tested as a mediator of the association between activation of threat-sensitive brain regions to social rejection and carotid plaque formation. In the second model, 7-day salivary IL-6 expression will be tested as mediator for the association of 7-day ecological momentary assessments (EMA) of everyday experiences of discrimination with carotid plaque formation. The reliability of these models of putative psycho-neuro-immune mechanisms in predicting carotid plaque burden will be assessed at baseline and 3-month follow-up. The study further aims to evaluate the potential mitigating role of the acetyl-cholinergic anti-inflammatory pathway on carotid plaque formation by testing whether an index of vagal-mediated heart rate variability (HRV) moderates of the associations of neural activation to rejection/discrimination (Aim 1) and naturalistic rejection/discrimination experiences (Aim 2) with change in proinflammatory cytokine expression. The long-term objectives of this study are two-fold. First, to elucidate the relationships amongst these biobehavioral determinants of carotid plaque formation in PWH, who are traditionally stigmatized and discriminated due to intersectionality of their race, ethnicity, gender, health, and sexual orientation status. The second long-term objective is to evaluate whether vagal-mediated HRV has a mitigating effect and thus serve as a target for future biobehavioral interventions for atherosclerotic CVD in PWH that have traditionally been socially marginalized, stigmatized and discriminated.