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HDL dysfunction: a role in the pathogenesis of cardiometabolic syndrome in chronic HIV infection?
Konstantinos Markakis1, Leila Fotooh Abadi2, Arnaud Kombe Kombe2
1First Department of Internal Medicine, Infectious Diseases Unit, AHEPA University Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Insights
People with HIV on antiretroviral therapy face higher cardiometabolic risks due to altered HDL function. Understanding this link is crucial for developing new treatments to improve cardiovascular health in this population.
Area of Science:
- Cardiovascular Medicine
- Infectious Diseases
- Metabolic Disorders
Background:
- People living with HIV (PLWH) on antiretroviral treatment (ART) exhibit increased risk for atherosclerotic cardiovascular disease (CVD) and metabolic syndrome, collectively termed cardiometabolic syndrome.
- Traditional CVD risk factors and alterations in high-density lipoproteins (HDL) contribute to this elevated risk.
- Assessing HDL function, rather than HDL cholesterol levels (HDL-C), may offer a more accurate measure of cardiometabolic risk.
Purpose of the Study:
- To review the scientific evidence on the role of HDL functions in HIV infection.
- To explore how therapeutic targeting of HDL dysfunction could reduce cardiometabolic risk in PLWH.
- To investigate the unclear impact of altered HDL functions on PLWH and the potential bidirectional crosstalk with cardiometabolic syndrome.
Main Methods:
- This review synthesizes existing scientific literature and evidence.
- It examines the effects of HIV-1, ART, and organ dysfunction on HDL proteome, lipidome, and metabolism.
- The review discusses the need for large cohorts with independent assays of HDL function to study the interplay between HDL function and cardiometabolic syndrome.
Main Results:
- HIV infection and ART significantly alter HDL metabolism and function, leading to HDL dysfunction.
- HDL dysfunction in PLWH is linked to increased cardiometabolic risk, though the exact nature of this relationship (reflective or contributory) requires further elucidation.
- Current understanding suggests a complex interplay between HDL function and cardiometabolic syndrome in the context of HIV.
Conclusions:
- Altered HDL function is a key factor in the elevated cardiometabolic risk observed in PLWH.
- Further research using robust methodologies is necessary to fully understand the bidirectional relationship between HDL function and cardiometabolic syndrome in HIV.
- Developing therapies to improve HDL function holds promise for mitigating chronic inflammation and reducing cardiometabolic risk in PLWH.
Abstract:
People living with human immunodeficiency virus (HIV) (PLWH) on antiretroviral treatment (ART) have an increased risk of atherosclerotic cardiovascular disease (CVD) and metabolic syndrome (combinations of adiposity, insulin resistance, hypertension, and dyslipidemia). Together, CVD and metabolic syndrome constitute the cardiometabolic syndrome. Traditional CVD risk factors and high-density lipoproteins (HDL) alterations seem to contribute to the elevated CVD risk. Cumulative evidence suggests that assessing HDL function instead of HDL cholesterol levels (HDL-C) may be a better way to assess cardiometabolic risk. In HIV infection, HIV-1, ART, and the altered function of organs like the liver, gastrointestinal tract, and immune system affect the proteome, lipidome, and metabolism of HDL, ultimately leading to its dysfunction. However, the impact of altered HDL functions on PLWH remains unclear and whether HDL dysfunction reflects and/or contributes to cardiometabolic syndrome in HIV infection (bidirectional cross talk regarding how HDL function impacts the cardiometabolic syndrome and vice versa). Large cohorts of PLWH with variable CVD risk using independent assays of HDL function are needed to elucidate the bidirectional crosstalk between HDL functions and cardiometabolic syndrome. Developing novel treatments to improve HDL function in PLWH may have multiple beneficial results, reducing chronic inflammation and cardiometabolic risk in PLWH. This review aims to summarize the scientific evidence related to the role of HDL functions in HIV and how therapeutic targeting of HDL dysfunction may contribute to reduced cardiometabolic risk in PLWH.
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