Abstract 4361420: Systemic Mitochondrial Function in Young Adults with Perinatal HIV Exposure and Infection with Cardiac Inflammatory Biomarkers and Echocardiogram Parameters

Abstract

Introduction: Children with perinatally-acquired HIV (PHIV) are now reaching adulthood due to improved antiretroviral treatment (ART); however, the cardiac comorbidities associated with altered mitochondrial (mt) function continue to raise significant concerns. Hypothesis: Mt measurements will correlate with echocardiographic measures (EM) of left ventricular function and structure, and with cardiac and inflammatory biomarkers (CIBs). Young adults with PHIV (YAPHIV) will exhibit lower mt DNA (mtDNA) copies per cell and higher systemic respiration rates than perinatally HIV-exposed but uninfected (YAPHEU). Aims: To determine the significance of systemic mitochondrial dysfunction in cardiovascular abnormalities and biomarkers, we assessed mtDNA copies/cell, respiration, and CIBs in a cross-sectional study. Methods: We assayed mtDNA copies/cell and mt respiration in viable peripheral blood mononuclear cells (PBMCs) by PCR and oximetry. We measured 10 CIBs: Interleukin [IL]-1β, IL-6, IL-8, IL-10, IL-18, tumor necrosis factor-α, soluble TNF receptor 2, Troponin T, NT-proBNP, and hs-CRP in plasma by ELISA. Cardiomyopathy was 2D LV ejection fraction z-score < -2. We calculated Spearman correlations among mt parameters, EM of left ventricular structure and function, and CIBs. In YAPHIV, linear regression models were fit using generalized estimation equations (GEEs) for enhanced robustness to assess the association of HIV disease severity and ART measures with mt parameters. Results: 153 participants were included (96 YAPHIV and 57 YAPHEU; median age 23.4 years; 60% female; 71% Black; 24% Hispanic). The median mt parameters showed no significant differences by HIV infection status. Weak correlations (p <0.20) were found between mt parameters, EM, and CIBs. In adjusted models, higher levels of IL-8 were linked to lower ATP production and lower basal respiration. Among YAPHIV, a nadir CD4% <15 was associated with lower basal respiration, maximal respiration, and ATP production. A longer duration on protease inhibitor (PI)-based ART correlated with lower spare respiratory capacity, while an extended duration on integrase strand transfer inhibitors was associated with higher spare respiratory capacity. Among 10 YAPHIV participants with the highest respiration levels, 3 had cardiomyopathy. Conclusion: We found no differences in mt parameters based on HIV status. Among 10 YAPHIV with high systemic oxygen consumption, a few exhibited cardiomyopathy, suggesting long-term consequences.