Role of T-Cell Dysfunction, Inflammation, and Coagulation in Microvascular Disease in HIV

Background--Compared to uninfected adults, HIV-infected adults on antiretroviral therapy are at increased risk of cardiovascular disease. Given the increase in T-cell dysfunction, inflammation, and coagulation in HIV infection, microvascular dysfunction is thought to contribute to this excess cardiovascular risk. However, the relationships between these variables remain undefined. Methods and Results--This was a cross-sectional study of 358 HIV-infected adults from the SCOPE cohort. Macrovascular endothelial function was assessed using flow-mediated dilation of the brachial artery and microvascular function by reactive hyperemia. T-cell phenotype was determined by flow cytometry. Plasma markers of inflammation (tumor necrosis factor-a, interleukin-6, high-sensitivity C-reactive protein, sCD14) and coagulation (fibrinogen, D-dimer) were also measured. In all HIV+ subjects, markers of inflammation (tumor necrosis factor-a, high-sensitivity C-reactive protein), coagulation (D-dimer) and T-cell activation (CD8+ PD1+, CD4+ interferon+ cytomegalovirus-specific) were associated with worse reactive hyperemia after adjusting for traditional cardiovascular risk factors and co-infections. In treated and suppressed subjects, tumor necrosis factor-a and CD8+ PD1+ cells remained associated with worse reactive hyperemia after adjustment. Compared to the untreated subjects, CD8+ PD1+ cells were increased in the virally suppressed group. Reactive hyperemia was predictive of flow-mediated dilation. Conclusions--CD8+ PD1+ cells and tumor necrosis factor-a were associated with microvascular dysfunction in all HIV+ subjects and the treated and suppressed group. Additionally, D-dimer, high-sensitivity C-reactive protein, sCD-14, and interleukin-6 were associated with microvascular dysfunction in all HIV+ subjects. Although T-cell dysfunction, inflammation, and microvascular dysfunction are thought to play a role in cardiovascular disease in HIV, this study is the first to look at which T-cell and inflammatory markers are associated with microvascular dysfunction in HIV-infected individuals.