Factors Associated With Systemic Immune Activation Indices in a Global Primary Cardiovascular Disease Prevention Cohort of People With Human Immunodeficiency Virus on Antiretroviral Therapy

Abstract

BACKGROUND Among ART-treated people with HIV (PWH), persistent systemic immune activation contributes to atherogenesis, cardiovascular disease (CVD) events, and mortality. Factors associated with key immune activation indices have not previously been characterized among a global primary CVD prevention cohort of PWH. METHODS Leveraging baseline REPRIEVE data, we interrogated factors associated with soluble CD14 (sCD14) and oxidized LDL (oxLDL). RESULTS The primary analysis cohort included 4,907 from 5 Global-Burden-of-Disease regions (38% female; 48% Black; median age 50y). When levels of sCD14 and oxLDL were characterized by sex, age, and region, female sex and residence in South Asia or Sub-Saharan Africa were associated with higher sCD14 levels while residence in high-income regions was associated with higher oxLDL levels. In fully adjusted models for sCD14, female sex and white race (among those in high-income regions) were associated with higher sCD14 levels while higher BMI and current use of NRTI+INSTI ART were associated with lower sCD14 levels. In fully adjusted models for oxLDL, male sex, residence in high-income regions, white race (among those in high-income regions), and higher BMI were associated with higher oxLDL levels. In a sub-analysis cohort of 1396 women with HIV, increased reproductive age was associated with higher sCD14 levels but not with higher oxLDL levels. CONCLUSIONS Factors associated with oxLDL and sCD14, two key indices of immune-mediated CVD risk, differ. Future studies will elucidate ways in which medications (e.g. statins) and behavioral modifications influence sCD14/oxLDL and the extent to which dampening of these markers mediates CVD-protective effects.

Persistent immune activation and altered gut integrity over time in a longitudinal study of Ugandan youth with perinatally acquired HIV

“…OxLDL is associated with coronary heart disease in adults ( 27 , 28 ). In the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), the largest primary CVD prevention trial in HIV, higher levels of oxLDL was associated with male sex, residence in high-income regions, white race and higher BMI ( 29 ). These findings highlight how there might be differences in systemic immune pathways in the global North and South.…”

“…Our findings highlight non-HIV sources of inflammation that are likely endemic to Sub-Saharan Africa. Exposure to multiple co-occurring adversities likely influence inflammation in this setting and may include exposure to social adversity, such as economic hardship, food insecurity, chronic stress ( 30 – 34 ) and exposure to environmental adversity, such as ambient air pollution – which has been increasing in SSA over the past decade ( 29 ) – has also been linked to inflammation ( 35 ). Although acute co-infections were exclusionary in this study, both groups in this study were exposed to high levels of economic insecurity, and PHIV were more likely to lack access to clean water and electricity.…”

Trans women have worse cardiovascular biomarker profiles than cisgender men independent of hormone use and HIV serostatus

“…A sexual dimorphism in sCD14 levels has been documented, with higher levels generally observed in people assigned female at birth that are not greatly affected by menopause [48]. Additionally, in one study of transgender people, feminizing therapies increased vWF whereas testosterone treatment decreased vWF levels [49].…”

Ideal cardiovascular health, biomarkers, and coronary artery disease in persons with HIV

“…High-sensitivity C-reactive protein (hsCRP) assays were performed at Quest Diagnostics. Assay limits and variability have been previously published [ 22 , 31 ].…”