Abstract
Combination antiretroviral therapy (ART) is effective at suppressing HIV viremia to achieve persistently undetectable levels in peripheral blood in the majority of individuals with access and ability to maintain adherence to treatment. However, evidence suggests that ART is less effective at eliminating HIV-associated inflammation and innate immune activation. To the extent that residual inflammation and immune activation persist, virologically suppressed people living with HIV (PLWH) may have increased risk of inflammatory co-morbidities, and adjunctive therapies may need to be considered to reduce HIV-related inflammation and fully restore the health of virologically suppressed HIV+ individuals. Cardiovascular disease (CVD) is the single leading cause of death in the developed world and is becoming more important in PLWH with access to ART. Arterial disease due to atherosclerosis, leading to acute myocardial infarction (AMI) and stroke, is a major component of CVD. Atherosclerosis is an inflammatory disease, and epidemiological comparisons of atherosclerosis and AMI show a higher prevalence and suggest a greater risk in PLWH compared to the general population. The reasons for greater prevalence of CVD in PLWH can be broadly grouped into four categories: (a) the higher prevalence of traditional risk factors e.g., smoking and hypertension (b) dyslipidemia (also a traditional risk factor) caused by off-target effects of ART drugs (c) HIV-related inflammation and immune activation and (d) other undefined HIV-related factors. Management strategies aimed at reducing the impact of traditional risk factors in PLWH are similar to those for the general population and their effectiveness is currently being evaluated. Together with improvements in ART regimens and guidelines for treatment, and a greater awareness of its impact on CVD, the HIV-related risk of AMI and stroke is decreasing but remains elevated compared to the general community. Monocytes are key effector cells which initiate the formation of atherosclerotic plaques by migrating into the intima of coronary arteries and accumulating as foam cells full of lipid droplets. This review considers the specific role of monocytes as effector cells in atherosclerosis which progresses to AMI and stroke, and explores mechanisms by which HIV may promote an atherogenic phenotype and function independent of traditional risk factors. Altered monocyte function may represent a distinct HIV-related factor which increases risk of CVD in PLWH.
Highlights
For PLWH at the present time, HIV infection is associated with different outcomes depending on access to care and treatment
It is important to consider that the pro-atherogenic phenotype of monocytes from virologically suppressed HIV-positive individuals revealed using the atherosclerotic plaque model is evident in the absence of added exogenous lipid or lipoprotein particles
We have used the same model to show that transmigrated monocytes can be induced to differentiate into foam cells by the addition of known atherogenic lipids such as Oxidized LDL (oxLDL) [124] and by LPS [127] into the culture medium
Summary
For PLWH at the present time, HIV infection is associated with different outcomes depending on access to care and treatment. Large cohort studies of persons from the United States, and from North America and Western Europe, have shown that the gap in life expectancy between PLWH and HIV-negative individuals has narrowed as a function of the year in which ART was initiated [2, 6].
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