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BackgroundOver the past four decades, advances in HIV treatment have contributed to a longer life expectancy for people living with HIV (PLWH). With these gains, the prevention and management of chronic co-morbidities, such as diabetes, are now central medical care goals for this population. In the United States, food insecurity disproportionately impacts PLWH and may play a role in the development of insulin resistance through direct and indirect pathways. The Nutrition to Optimize, Understand, and Restore Insulin Sensitivity in HIV for Oklahoma (NOURISH-OK) will use a novel, multi-level, integrated framework to explore how food insecurity contributes to insulin resistance among PLWH. Specifically, it will explore how food insecurity may operate as an intermediary risk factor for insulin resistance, including potential linkages between upstream determinants of health and downstream consequences of poor diet, other behavioral risk factors, and chronic inflammation.Methods/designThis paper summarizes the protocol for the first aim of the NOURISH-OK study, which involves purposeful cross-sectional sampling of PLWH (n=500) across four levels of food insecurity to test our conceptual framework. Developed in collaboration with community stakeholders, this initial phase involves the collection of anthropometrics, fasting blood samples, non-blood biomarkers, 24-hour food recall to estimate the Dietary Inflammatory Index (DII®) score, and survey data. A 1-month, prospective observational sub-study (total n=100; n=25 for each food security group) involves weekly 24-hour food recalls and stool samples to identify temporal associations between food insecurity, diet, and gut microbiome composition. Using structural equation modeling, we will explore how upstream risk factors, including early life events, current discrimination, and community food access, may influence food insecurity and its potential downstream impacts, including diet, other lifestyle risk behaviors, and chron