Cardiovascular disease (CVD) is emerging as a major threat to healthy aging among people with HIV (PHIV). PHIV face heightened risks for coronary heart disease (CHD)/myocardial infarction (MI) and heart failure (HF), fueled by systemic immune activation and by metabolic dysregulation. Women with HIV (WHIV) evidence unique patterns of vascular and myocardial pathology as compared to men with HIV (MHIV). These patterns include a predilection to microvascular dysfunction and type II MI, as well as a penchant for diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF). Investigations are underway to understand how advanced reproductive aging among WHIV influences systemic immune activation and metabolic dysregulation en route to these CVD phenotypes. A key goal is to identify targeted CVD prevention strategies relevant to WHIV, particularly as efficacious treatment approaches to type II MI and HFpEF are lacking.