7. Project Summary/Abstract US women living with HIV (WLHIV) on antiretroviral therapy (ART) face a three-fold risk of myocardial infarction (MI) compared with women without HIV. Further, among WLHIV who present with MI, the majority (56%) present with type 2 MI – oxygen supply/demand mismatch in the absence of atherothrombosis. Data suggest that coronary microvascular dysfunction and excess epicardial adipose tissue (EAT) volume represent salient processes relevant to type 2 MI risk among WLHIV. Our team aims to identify novel salutary interventions. We propose a randomized controlled trial assessing the effect of sodium glucose transporter 2 (SGLT2) inhibitors on cardiac PET-derived coronary flow reserve (a CV risk surrogate reflecting the ability to augment blood flow through large and small coronary arteries) and cardiac CT-derived EAT among WLHIV. SGLT2 inhibitors, originally developed to treat DM2, work by blocking renal sodium/glucose reabsorption, leading to glucosuria, as well as reduced glomerular perfusion pressure. Kidney- and cardio-protective effects of SGLT2 inhibitors led to approval for use in CKD and heart failure, even among those without DM2. SGLT2 inhibition has been shown to improve coronary flow reserve and EAT in some patient populations but not others. The observation that effects are population-specific highlights the need for testing among at-risk WLHIV. Notably, newly published work from our group suggests SGLT2 inhibitors are rarely prescribed to PLHIV with clinical indications in a large US healthcare system: <9% of PLHIV with DM2 and <4% of PLHIV with DM2 and CKD. Randomizing WLHIV with a clinical indication (DM2, CKD, or both) to either SGLT2 inhibitor therapy + health education or health education alone x 24 weeks, we will: 1) Characterize effects of SGLT2 inhibition on coronary flow reserve; 2) Characterize effects of SGLT2 inhibition on EAT; 3) Assess whether changes in coronary flow reserve and EAT are predicted by baseline values of and/or associated with changes in key kidney, metabolic, inflammatory parameters. Our central hypothesis is that SGLT2 inhibition + health education vs. health education alone will result in a relative increase in coronary flow reserve and reduction in EAT. Our work will likely identify a viable strategy to increase coronary flow reserve and reduce EAT among WLHIV at risk for type 2 MI. Because this strategy is clinically available but underutilized among WLHIV, evidence on favorable population-specific effects will be particularly informative. If SGLT2 inhibition increases coronary flow reserve and/or reduces EAT among WLHIV, our work will yield mechanistic insights into whether improvements relate to changes in kidney, metabolic, and immune/inflammatory parameters. Even if SGLT2 inhibition yields disappointing results, our identification of novel factors associated with decline in coronary flow reserve and/or increase in EAT among WLHIV will suggest alternate strategies to improv...