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Background: In HIV-uninfected populations, physical activity decreases mortality and inflammation. Inflammation is a potential cause of comorbidities in HIV+ adults, the evidence examining the effect of physical activity on cardiometabolic health is limited. This analysis examines the relationship between physical activity, cardiometabolic health and inflammation., Methods: We conducted a nested study within the SATURN-HIV trial in which 147 HIV+ adults were randomized to 10 mg daily rosuvastatin or placebo. Measures of physical activity, cardiometabolic health, inflammation and vascular disease (carotid artery intima media thickness and computed tomography-acquired measures pericardial fat volume) were assessed at baseline and through 96 weeks. Spearman correlations and multivariable analyses were used to explore relationships between physical activity, cardiometabolic health and inflammation., Results: Median age (Q1, Q3) was 46 (40.4, 52.7) years, 80% were male, 69% were African American and 46% were on protease inhibitors. Baseline median physical activity was 44 min per week (0, 150), 24% of participants performed greater than 150 min per week. At baseline, physical activity correlated with several markers of cardiometabolic health and inflammation (all P≤0.05). Over all time points median physical activity was independently associated with carotid distensibility (β=2.53; P=0.008), pericardial fat volume (β=-6.13; P=0.001) and interleukin-6 (β=-0.468; P<0.001)., Conclusions: Physical activity is associated with vascular disease, endothelial function, and may be an adjuvant to decreasing comorbidities in HIV+ adults. Further studies should examine long-term effects of physical activity on cardiometabolic health and inflammation in this population. Clinicaltrials.gov NCT01218802.