Monocytes from men living with HIV exhibit heightened atherogenic potential despite long-term viral suppression with antiretroviral therapy

• Published in: AIDS (London) Vol. 34; no. 4; pp. 513 - 518
• Main Authors: Angelovich, Thomas A, Trevillyan, Janine M, Hoy, Jennifer F, Wong, Michelle E, Agius, Paul A, Hearps, Anna C, Jaworowski, Anthony
• Format: Journal Article
• Language: English
• Published: England Copyright Wolters Kluwer Health, Inc 15.03.2020
• Subjects: Adult; Aged; AIDS/HIV; Antiretroviral Therapy, Highly Active; Atherosclerosis - etiology; Atherosclerosis - metabolism; Atherosclerosis - pathology; Cardiovascular Diseases - etiology; Cardiovascular Diseases - metabolism; Carotid Intima-Media Thickness; Cross-Sectional Studies; Foam Cells - immunology; Foam Cells - metabolism; Foam Cells - pathology; HIV Infections - complications; HIV Infections - drug therapy; HIV Infections - virology; Humans; Inflammation - pathology; Linear Models; Male; Middle Aged; Monocytes - immunology; Monocytes - metabolism; Risk Factors
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/QAD.0000000000002460

OBJECTIVE:People living with HIV have an increased risk of cardiovascular disease (CVD) despite effective antiretroviral therapy (ART). Monocytes play a key role in the early stages of atherosclerosis-driven CVD by forming lipid-laden foam cells within artery walls. HIV infection potentiates foam cell formation ex vivo, but the mechanisms contributing to this are not known. METHODS:We investigated the atherosclerosis-promoting potential of monocytes from 39 virologically suppressed men living with HIV (MLHIV) on ART and no evidence of CVD, and 25 HIV-uninfected controls of comparable age, sex, smoking status and CVD risk. RESULTS:Despite absence of clinical atherosclerosis in both MLHIV and uninfected cohorts (evidenced by a carotid intima–media thickness of 0.6 mm for both groups; P = 0.254), monocytes from MLHIV showed increased potential to form atherosclerosis-promoting foam cells compared with controls in an ex-vivo assay (36.6% vs. 27.6%, respectively, P = 0.003). Consistent with observations of persistent inflammation and immune/endothelial activation in ART-treated HIV infection, levels of soluble tumour necrosis factor receptor II, CXCL10 and soluble VCAM-1 were elevated in MLHIV (P ≤ 0.005 for all), but were not significantly associated with foam cell formation. Foam cell formation was associated with an impaired ability of monocytes to undergo reverse transmigration, and a reduced ability to efflux cholesterol ex vivo (P < 0.05 for both). Importantly, foam cell formation declined significantly with duration of viral suppression (P = 0.004). CONCLUSION:These findings highlight the persistence of HIV-related changes to the atherogenic potential of monocytes despite long-term viral suppression, and provide insights into mechanisms potentially driving increased CVD in ART-treated HIV infection.