A Blood Immunological Signature of Subclinical Coronary Artery Atherosclerosis in People Living with HIV-1 Receiving Antiretroviral Therapy

Wiche Salinas, T. R.; Zhang, Y.; Gosselin, A.; Fonseca Do Rosario, N.; El-Far, M.; Filali-Mouhim, A.; Routy, J.-P.; Chartrand-Lefebvre, C.; Landay, A. L.; Durand, M.; Tremblay, C.; Ancuta, P.

doi:10.1101/2023.12.15.571922

bioRxiv · 10.1101/2023.12.15.571922

A Blood Immunological Signature of Subclinical Coronary Artery Atherosclerosis in People Living with HIV-1 Receiving Antiretroviral Therapy

Wiche Salinas, T. R.·Zhang, Y.·Gosselin, A.·Fonseca Do Rosario, N.·El-Far, M.·Filali-Mouhim, A.·Routy, J.-P.·Chartrand-Lefebvre, C.·Landay, A. L.·Durand, M.·Tremblay, C.·Ancuta, P.

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Abstract

Cardiovascular disease (CVD) remains an important co-morbidity in people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Our previous studies performed on the Canadian HIV/Aging Cohort Study (CHACS) (>40 years-old; Framingham Risk Score (FRS) >5%), revealed a 2-3-fold increase in non-calcified coronary artery atherosclerosis (CAA) plaque burden, measured by Computed tomography angiography scan (CTAScan) as total (TPV) and low attenuated plaque volume (LAPV) in ART-treated PLWH (HIV+) versus uninfected controls (HIV-). In an effort to identify novel correlates of subclinical CAA, markers of intestinal damage (sCD14, LBP, FABP2); cell trafficking/inflammation (CCL20, CX3CL1, MIF, CCL25); subsets of Th17-polarized and regulatory (Tregs) CD4+ T-cells, classical/intermediate/non-classical monocytes, and myeloid/plasmacytoid dendritic cells, were studied in relationship with HIV and TPV/LAPV status. The TPV detection/values coincided with higher plasma sCD14, FABP2, CCL20, MIF, CX3CL1 and triglyceride levels, lower Th17/Treg ratios, and classical monocyte expansion. Among HIV+, TPV+ versus TPV- exhibited lower Th17 frequencies, reduced Th17/Treg ratios, higher frequencies of non-classical CCR9lowHLADRhigh monocyte, and increased plasma fibrinogen levels. Finally, Th17/Treg ratios and non-classical CCR9lowHLADRhigh monocyte frequencies remained associated with TPV/LAPV after adjusting for FRS and HIV/ART duration in a logistic regression model. These findings point to Th17 paucity and non-classical monocyte abundance as novel immunological correlates of subclinical CAA that may fuel the CVD risk in ART-treated PLWH.

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Wiche Salinas, T. R., Zhang, Y., Gosselin, A., Fonseca Do Rosario, N., El-Far, M., Filali-Mouhim, A., Routy, J.-P., Chartrand-Lefebvre, C., Landay, A. L., Durand, M., Tremblay, C., Ancuta, P.. 2023-12-18. A Blood Immunological Signature of Subclinical Coronary Artery Atherosclerosis in People Living with HIV-1 Receiving Antiretroviral Therapy. https://doi.org/10.1101/2023.12.15.571922

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