Publications & Reports

Monocytes from men living with HIV exhibit heightened atherogenic potential despite long term viral suppression with ART.

Angelovich TA, Trevillyan JM, Hoy JF, Wong ME, Agius PA, Hearps AC, Jaworowski A
Healthy Ageing Program, Burnet Institute, Melbourne, Victoria 3004, Australia.


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 to 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 TNF 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). CONCLUSIONS: 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.

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