Background
Few data exist on inflammatory markers and their association with myocardial fibrosis and inflammation in youth with HIV (YHIV).
Methods
The Cape Town Adolescent and Antiretroviral Cohort (CTAAC)-Heart study enrolled youth with perinatally acquired HIV (YPHIV), with non-perinatally acquired HIV (YNPHIV) and HIV-seronegative youth (HIV-) and performed cardiovascular magnetic resonance (CMR) to assess cardiac fibrosis [late gadolinium enhancement (LGE) mass and fraction, extracellular volume (ECV)] and inflammation [native T1 and T2 mapping] outcomes. Markers of inflammation [C-reactive protein (CRP), interleukin-6 (IL6), tumor necrosis factor-alpha (TNF-a)] and immune activation [soluble (s)CD14, sCD163], cardiac injury [N-terminal pro-B-type natriuretic peptide (NT-proBNP), soluble ST-2] and fibrosis (galectin), and vascular activation [intercellular adhesion molecule (ICAM1)] were measured via ELISA. Quantile regression models were fit with an interaction term between HIV status and each marker to assess for effect modification by HIV status on CMR outcomes.
Results
273 YPHIV, 74 YNPHIV, and 72 HIV- were included; 56% were female. Median age and BMI were highest among YNPHIV compared to YPHIV and HIV- (20 vs. 18 and 17 years; 26 vs 22 and 22 kg/m2, respectively). Among YHIV, a lower proportion of YPHIV vs. YNPHIV had a CD4 >500 cells/mm3 (57 vs. 62%) or were on integrase inhibitors (33 vs. 87%). Overall sCD14 (1934 vs. 1926 and 1759 ng/mL, p=0.002) and TNF-a (9.5 vs. 8.9 and 9.2 pg/mL, p=0.021) were highest in YPHIV vs. YNPHIV and HIV-; CRP (3001 vs. 1611 and 889 ng/mL, p=0.006) and galectin (6.7 vs. 5.5 and 5.5 ng/mL, p<0.001) were highest in YNPHIV vs. YPHIV and HIV-. HIV status significantly modified the associations of TNF-a with LGE mass (p<0.001) and native T1 (p=0.011) after adjusting for age, female sex, body surface area, prior tuberculosis, and systolic blood pressure. (Figure 1) In addition, HIV status modified the effect of IL6 on native T1 (p<0.001). There was no effect modification by HIV status on associations of all other biomarkers with CMR outcomes.
Conclusions
While markers of inflammation, immune activation, and cardiac fibrosis appear to be higher in YHIV compared to HIV-, relationships of some inflammatory markers on cardiac fibrosis and inflammation are significantly different between YPHIV, YNPHIV, and HIV-. Future studies are warranted to assess markers most predictive of cardiac fibrosis and inflammation in YHIV.
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