Abstract
Background: We aimed to investigate whether circulating microparticle (CMPs) subsets were raised amongst people presenting with human immunodeficiency virus (HIV) and advanced immune suppression in Malawi, and whether they associated with arterial stiffness. Methods: Antiretroviral therapy (ART)-naïve adults with a new HIV diagnosis and CD4 <100 cells/µL had microparticle characterisation and carotid femoral Pulse Wave Velocity (cfPWV) at 2 weeks post ART initiation. HIV uninfected controls were matched on age, systolic blood pressure (BP) and diastolic BP in a 1:1 ratio. Circulating microparticles were identified from platelet poor plasma and stained for endothelial, leucocyte, monocyte and platelet markers. Results: The median (IQ) total CMP count for 71 participants was 1 log higher in HIV compared to those without (p<0.0001) and was associated with arterial stiffness (spearman rho 0.47, p<0.001). In adjusted analysis, every log increase in circulating particles showed a 20% increase in cfPWV (95% confidence interval [CI] 4 - 40%, p=0.02). In terms of subsets, endothelial and platelet derived microparticles were most strongly associated with HIV. Endothelial derived E-selectin+ CMPs were 1.3log-fold higher and platelet derived CD42a+ CMPs were 1.4log-fold higher (both p<0.0001). Endothelial and platelet derived CMPs also correlated most closely with arterial stiffness (spearman rho: E-selectin+ 0.57 and CD42a 0.56, both p<0.0001). Conclusions: Circulating microparticles associate strongly with arterial stiffness among people living with HIV in Malawi. Endothelial damage and platelet microparticles are the predominant cell origin types and future translational studies could consider prioritising these pathways.
Highlights
People living with human immunodeficiency virus (HIV) (PLWH) are at increased risk of cardiovascular diseases1–4
Here we show that total Circulating microparticles (CMPs) correlate closely with arterial stiffness and are markedly increased amongst people who present with HIV and advanced immune suppression in Malawi
Microparticles originating from endothelium and platelets were especially high amongst people with HIV and correlated strongly with arterial stiffness; suggesting that these pathways might be prioritised for future studies seeking to reduce inflammation driven cardiovascular risk amongst PLWH during Antiretroviral therapy (ART) initiation
Summary
People living with human immunodeficiency virus (HIV) (PLWH) are at increased risk of cardiovascular diseases. We have previously shown that amongst people presenting with HIV and a CD4 count less than 100 cells/mm, arterial stiffness is increased by 12% (adjusted fold change) compared to healthy volunteers living without HIV5. Arterial stiffness has been used as a measure of vascular dysfunction in HIV studies as well as other chronic inflammatory conditions and we have previously shown that arterial stiffness, as measured by carotid femoral pulse wave velocity (cfPWV), is increased in people experiencing unstructured treatment interruption. We aimed to investigate whether circulating microparticle (CMPs) subsets were raised amongst people presenting with human immunodeficiency virus (HIV) and advanced immune suppression in Malawi, and whether they associated with arterial stiffness. Every log increase in circulating particles showed a 20% increase in cfPWV (95% confidence interval [CI] 4 – 40%, p=0.02)
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