Design: HIV-infected (HIVþ) individuals have an increased risk of atherosclerosis and
cardiovascular disease which is independent of antiretroviral therapy and traditional
risk factors. Monocytes play a central role in the development of atherosclerosis, and
HIV-related chronic inflammation and monocyte activation may contribute to
increased atherosclerosis, but the mechanisms are unknown.
Methods: Using an in-vitro model of atherosclerotic plaque formation, we measured
the transendothelial migration of purified monocytes from age-matched HIVþ and
uninfected donors and examined their differentiation into foam cells. Cholesterol efflux
and the expression of cholesterol metabolism genes were also assessed.
Results: Monocytes from HIVþ individuals showed increased foam cell formation
compared with controls (18.9 vs. 0%, respectively, P¼0.004) and serum from virologically
suppressed HIVþ individuals potentiated foam cell formation by monocytes
from both uninfected and HIVþ donors. Plasma tumour necrosis factor (TNF) levels
were increased in HIVþ vs. control donors (5.9 vs. 3.5 pg/ml, P¼0.02) and foam cell
formation was inhibited by blocking antibodies to TNF receptors, suggesting a direct
effect on monocyte differentiation to foam cells. Monocytes from virologically suppressed
HIVþ donors showed impaired cholesterol efflux and decreased expression of
key genes regulating cholesterol metabolism, including the cholesterol transporter
Conclusion: Monocytes from HIVþ individuals show impaired cholesterol efflux and
are primed for foam cell formation following transendothelial migration. Factors present
in HIVþ serum, including elevated TNF levels, further enhance foam cell formation.
The proatherogenic phenotype of monocytes persists in virologically suppressed HIVþ
individuals and may contribute mechanistically to increased atherosclerosis in this