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. 2016 Dec 20;5(12):e004243.
doi: 10.1161/JAHA.116.004243.

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

Arjun Sinha  1 , Yifei Ma  2 , Rebecca Scherzer  2 , Sophia Hur  3 , Danny Li  3 , Peter Ganz  3 , Steven G Deeks  4 , Priscilla Y Hsue  5
Affiliations

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

Arjun Sinha et al. J Am Heart Assoc. .

Abstract

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-α, 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-α, 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-α 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-α 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.

Keywords: HIV; coagulation; immune system; inflammation; microcirculation.

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Figures

Figure 1
Figure 1
The role of T‐cell dysfunction, inflammation, and coagulation in microvascular and macrovascular dysfunction in HIV‐infected adults. CMV indicates cytomegalovirus; FMD, flow‐mediated dilation; hsCRP, high‐sensitivity C‐reactive protein; IL‐6, interleukin‐6; TNF‐α, tumor necrosis factor‐α.
See this image and copyright information in PMC

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