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Background Biomarkers of myocardial stress and fibrosis are elevated in people living with HIV and are associated with cardiac dysfunction. It is unknown whether sex influences these markers of heart failure risk in sub‐Saharan Africa, where HIV burden is high and where the vast majority of women with HIV live. Methods and Results Echocardiograms and 6 plasma biomarkers (suppression of tumorigenicity‐2, growth differentiation factor 15, galectin 3, soluble fms‐like tyrosine kinase‐1, NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide], and cystatin C) were obtained from 100 people living with HIV on antiretroviral therapy and 100 HIV‐negative controls in Uganda. All participants were ≥45 years old with ≥1 major cardiovascular risk factor. Multivariable linear and logistic regression models were used to assess associations between biomarkers, echocardiographic variables, HIV status, and sex, and to assess whether sex modified these associations. Overall, mean age was 56 years and 62% were women. Suppression of tumorigenicity‐2 was higher in men versus women (P &lt;0.001), and growth differentiation factor 15 was higher in people living with HIV versus controls (P &lt;0.001). Sex modified the HIV effect on cystatin C and NT‐proBNP (bothP for interaction &lt;0.025). Women had more diastolic dysfunction than men (P= 0.02), but there was no evidence of sex‐modifying HIV effects on cardiac structure and function. Cardiac biomarkers were more strongly associated with left ventricular mass index in men compared with women.Conclusions There are prominent differences in biomarkers of cardiac fibrosis and stress by sex and HIV status in Uganda. The predictive value of cardiac biomarkers for heart failure in people living with HIV in sub‐Saharan Africa should be examined, and novel risk markers for women should be further explored.

Sex, HIV Status, and Measures of Cardiac Stress and Fibrosis in Uganda