HIV disease, metabolic dysfunction and atherosclerosis: A three year prospective study

Abstract

HIV infection is known to be associated with cardiometabolic abnormalities; here we investigated the progression and causes of these abnormalities. Three groups of participants were recruited: HIV-negative subjects and two groups of treatment-naïve HIV-positive subjects, one group initiating antiretroviral treatment, the other remaining untreated. Intima-media thickness (cIMT) increased in HIV-positive untreated group compared to HIV-negative group, but treatment mitigated the difference. We found no increase in diabetes-related metabolic markers or in the level of inflammation in any of the groups. Total cholesterol, low density lipoprotein cholesterol and apoB levels were lower in HIV-positive groups, while triglyceride and Lp(a) levels did not differ between the groups. We found a statistically significant negative association between viral load and plasma levels of total cholesterol, LDL cholesterol, HDL cholesterol, apoA-I and apoB. HIV-positive patients had hypoalphalipoproteinemia at baseline, and we found a redistribution of sub-populations of high density lipoprotein (HDL) particles with increased proportion of smaller HDL in HIV-positive untreated patients, which may result from increased levels of plasma cholesteryl ester transfer protein in this group. HDL functionality declined in the HIV-negative and HIV-positive untreated groups, but not in HIV-positive treated group. We also found differences between HIV-positive and negative groups in plasma abundance of several microRNAs involved in lipid metabolism. Our data support a hypothesis that cardiometabolic abnormalities in HIV infection are caused by HIV and that antiretroviral treatment itself does not influence key cardiometabolic parameters, but mitigates those affected by HIV.

Exosomes containing HIV protein Nef reorganize lipid rafts potentiating inflammatory response in bystander cells

“…Finally, we compared exosomes isolated from plasma of uninfected volunteers and from HIV-infected subjects. Plasma was pooled from 4 uninfected and from 4 HIV-infected subjects undergoing treatment with ART and described in our recent study [19]. Exosomes from HIV-infected, ART treated donors (HIV+) reduced cholesterol efflux as well as abundance of total and cell-surface ABCA1 compared to exosomes from uninfected individuals (Fig 2I and 2J).…”

The Role of the ATP-Binding Cassette A1 (ABCA1) in Human Disease

“…In addition, recent studies have shown that Nef can be released from infected cells through extracellular vesicles altering cholesterol metabolism in uninfected recipient cells [237,[243][244][245]. It is well known that HIV patients develop dyslipidemia, and their HDL-C plasma concentrations can be as low as those of TD patients [60,246,247]. The Nef protein causes dyslipidemia, as it affects cholesterol efflux by reducing the expression of ABCA1 in in vitro and in vivo models [237,[248][249][250].…”

Lipids, biomarkers, and subclinical atherosclerosis in treatment-naive HIV patients starting or not starting antiretroviral therapy: Comparison with a healthy control group in a 2-year prospective study

“…The aims of this study were to investigate the effect of HIV infection and c-ART on LDL particle phenotype and atherogenesis-related biomarkers in a cohort of treatment-naïve HIV-infected patients and to assess the relationship between these variables and subclinical carotid atherosclerosis. The data we report can be added to findings published recently by our group on other atherogenesis-related pathways, mainly metabolism of HDL [ 26 ]. To our knowledge, no previous studies have compared biomarkers of cardiovascular disease in treatment-naïve HIV-infected patients starting or not starting c-ART and a healthy control group.…”