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

Abstract

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.

Carotid Ultrasound Abnormalities of People Living With HIV in Kunming, China: Multiple Correspondence Analysis Approach to Identify Influencing Factors

“…49 When PLWH are treated with protease inhibitors (PI), SCA occurs mainly by altering lipid metabolism and endothelial function. 50 Interestingly, even if patients are treated with ART, and the virus is suppressed, the effect of HIV on monocytes is still present in affected individuals than in unaffected individuals, affecting plaque formation, 51 thus leading to abnormal carotid ultrasounds.…”

Ultrasonic evaluation of carotid artery elasticity in People Living with HIV

“…Previous studies have confirmed that HAART is closely related to hypercholesterolemia, the increase of TG and LDL-c and the decrease of HDL-c [16 17 ].HAART can effectively inhibit the replication of HIV virus in PLWH, and significantly reduce the opportunistic infection and mortality of PLWH.On the one hand, clinical and experimental data show that inflammation plays an important role in atherosclerosi s [18] .However, HAART is less effective in eliminating HIV-related inflammation and innate immune activation. PLWH has a higher incidence of atherosclerosis than the general population.On the other hand, the side effects of antiretroviral drugs contribute to traditional CVD risk factors, including increased circulating levels of TC and TG, visceral obesity, and lower HDL-c levels [19 ].The mechanism of atherosclerosis caused by dyslipidemia is a hotspot of current research. HDL-C is one of the serum proteins that antagonize atherosclerosis,HDL-C carries the TC in the surrounding tissues, and then converts them into bile acids or is directly excreted from the intestine through bile.Studies have confirmed that there is a significant correlation between the decrease in HDL and the increase in the number of coronary artery stenosis in male patients [20] .In this study, HDL-c showed an increasing trend after HAART treatment, which was inconsistent with previous studies.…”

“…With the widespread use of HAART in many countries, the HIV/AIDS-related morbidity and mortality of PLWH have been significantly reduced. However, the special role of HIV and HAART drugs in promoting atherosclerosis significantly increases the risk of atherosclerotic cardiovascular disease (ASCVD) in PLWH [ 1,2] . ASCVD has become one of the important causes of PLWH's death.…”

Biomarkers to predict cardiovascular disease in people living with HIV

“…Circulating monocytes differentiate into macrophages upon migration into tissues, and by scavenging subendothelial lipoproteins can contribute to plaque regression through a process of reverse transendotheolial migration or plaque progression through the formation of foam cells, one of the main cellular constituents of vascular plaque. Angelovich et al [8 ▪ ] examined factors associated with foam cell formation from monocytes in a cohort of ART-treated, virally suppressed men living with HIV (MWH) and uninfected controls matched for age, sex and smoking status. Monocytes from MWH were 30% more likely to transmigrate and form foam cells compared with uninfected participants.…”