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

AIDS. 2020 Mar 15;34(4):513-518. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • 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