Abstract Background Few data exist on cardiac fibrosis and inflammation in youth with HIV, particularly in sub-Saharan Africa. Purpose Our objective was to assess the association between HIV status and cardiovascular magnetic resonance (CMR) measures of subclinical cardiac fibrosis, inflammation, and function. Methods We performed CMR on a cross-section of youth in South Africa: youth with perinatally acquired HIV (YPHIV), youth with non-perinatally acquired HIV (YNPHIV), and HIV-seronegative youth (YHIV-). Subclinical fibrosis late gadolinium enhancement (LGE) mass and fraction, extracellular volume (ECV), inflammation native T1 and T2 mapping, and cardiac function (cine, strain, and strain rate) were assessed. CD4, viral load (VL), and fasting glucose, insulin for Homeostatic Model Assessment-Insulin Resistance (HOMA) and lipids were obtained. Unadjusted and adjusted quantile regression models were used to assess the association between HIV status and CMR outcomes. In sub-group analyses of youth with HIV, we additionally adjusted for HIV factors. Results Of 464 youth, 287 were YPHIV, 87 YNPHIV, and 90 YHIV-. YNPHIV were older with a higher proportion self-identifying as female than YPHIV and YHIV- (median age 20 vs 18 and 17 years; 85% vs 50% and 49%, respectively). YPHIV had lower body surface area (1.6 vs 1.7 and 1.7m2) and a higher proportion with prior TB disease (70% vs. 20% vs 8%) compared to YNPHIV and YHIV-. Tobacco use, HOMA, total cholesterol, and low-density lipoproteins were similar between groups. Among youth with HIV, YPHIV had a higher proportion with CD4<200 cells/mm3 (10% vs 4%) or VL>50 copies/mL (39% vs 13%) but lower proportion on integrase inhibitors (33% vs 84%). LGE mass (0.13 vs 0.12 vs 0.07g respectively) and fraction (0.3% vs 0.3% vs. 0.2% respectively) were higher in YPHIV and YNPHIV than YHIV-; native T1 was highest in YNPHIV compared to YPHIV and YHIV- (Table). In adjusted analyses, compared to YHIV-, median LGE mass was higher in YPHIV and YNPHIV (β:0.06, p=0.01 for YPHIV, β:0.05, p=0.03 for YNPHIV) and LGE% was higher in YPHIV (β:0.14, p=0.02); native T1 and ECV did not differ between groups in adjusted analyses. Among youth with HIV, CMR outcomes did not differ significantly for persons with perinatal vs non-perinatal HIV. Findings did not vary in analyses restricted to females. Conclusion In one of the largest studies of CMR among youth with HIV in sub-Saharan Africa, we found that despite their young age, YPHIV and YNPHIV appear to have higher subclinical cardiac fibrosis than YHIV- and healthy adults in South Africa. Youth with HIV may benefit from early screening and long-term monitoring for cardiovascular disease.TableFigure