Background HIV infection and abacavir‐containing antiretroviral regimens are associated with vascular endothelial dysfunction and increased cardiovascular risk. Positron emission tomography (PET)‐derived myocardial blood flow reserve (MBFR), the ratio of vasodilator stress to rest myocardial blood flow, is a well‐validated measure of coronary microvascular health and marker of cardiovascular risk. Our objective was to compare MBFR among people with HIV (PWH) with matched non‐HIV controls and to assess whether switching from dolutegravir/lamivudine/abacavir to the non‐abacavir regimen bictegravir/emtricitabine/tenofovir alafenamide (TAF) would improve MBFR. Methods and Results Thirty‐seven PWH were 1:2 matched on cardiovascular risk factors to 75 people without HIV, and MBFR corrected for differences in resting hemodynamics was compared in a cross‐sectional design. PWH were majority men (68%) with a mean age of 56 years. Mean stress myocardial blood flow (1.83 mL/min per g [95% CI, 1.68–1.98] versus 2.40 mL/min per g [95% CI, 2.25–2.54]; P