Factors Associated with Systemic Immune Activation Indices in a Global Primary Cardiovascular Disease Prevention Cohort of People with HIV 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.