Atherosclerosis and cardiovascular risk in people living with HIV

HIV News: Recent advances in antiretroviral therapy (ART) have significantly improved the life expectancy of people living with HIV (PLWH). However, along with this increased longevity comes an elevated risk of chronic conditions, particularly cardiovascular disease (CVD). As more people with HIV live longer, researchers are keen to explore the complex relationship between HIV, ART, and cardiovascular health. This HIV News report aims to unravel how HIV contributes to atherosclerosis - a key precursor of CVD - and what can be done to mitigate these risks. This article delves into the key findings from a focused review on the intersection of HIV and cardiovascular complications.


Atherosclerosis and cardiovascular risk in people living with HIV

How HIV Increases Cardiovascular Risk
While atherosclerosis is commonly associated with high cholesterol and poor lifestyle choices, its development in PLWH is influenced by both traditional risk factors and HIV-specific mechanisms. According to researchers from the University of Messina and ARNAS Garibaldi Hospital in Italy, factors like chronic inflammation, immune activation, and the side effects of ART play a pivotal role in heightening cardiovascular risk in this population.
 
The study identifies several HIV-associated proteins, including Tat, Nef, and gp120, that exacerbate endothelial dysfunction and promote atherosclerosis. These proteins trigger a series of pathological changes in vascular tissues, increasing the likelihood of plaque formation, which can lead to serious cardiovascular events like heart attacks and strokes.
 
Understanding Atherosclerosis in HIV
Atherosclerosis, the build-up of plaques in the arterial walls, is a chronic condition that can have severe consequences. These plaques are prone to rupture, potentially leading to life-threatening events such as myocardial infarction and stroke. Research indicates that PLWH are more likely to develop atherosclerosis than their HIV-negative counterparts, even when other risk factors are taken into account.
 
The study highlights that in PLWH, the plaques formed in the coronary arteries tend to be non-calcified, making them more prone to rupture. This is particularly alarming because these plaques can lead to thrombotic events that significantly elevate the risk of mortality. Therefore, the monitoring and management of cardiovascular health in HIV patients is critical.
 
Chronic Inflammation and Immune Activation
Chronic inflammation is a hallmark of HIV, persisting even when viral replication is well-controlled with ART. The study identifies inflammation as a key driver of cardiovascular risk in PLWH. Inflammatory markers such as IL-6, TNF-α, and D-dimer remain elevated, which directly contributes to endothelial damage and plaque formation.
 
In addition to chronic inflammation, immune activation in PLWH also plays a significant role in cardiovascular health. Activated T cells and monocytes, which are commonly found in HIV-positive individuals, promote hypercoagulation and further damage to the arterial walls. These cells also maintain HIV reservoirs in the body, contributing to ongoing immune activation and the persistence of inflammation, even when viral suppression is achieved.
 
The Role of Antiretroviral Therapy (ART)
While ART has transformed HIV from a fatal disease into a manageable chronic condition, it also comes with its own set of challenges. Certain ART regimens, particularly older ones, have been linked to metabolic disturbances, such as dyslipidemia and insulin resistance, both of which are major risk factors for CVD.

Newer ART regimens, particularly those based on Integrase Strand Transfer Inhibitors (INSTIs), have shown better lipid profiles and are less likely to cause dyslipidemia compared to protease inhibitors (PIs). However, even with these advancements, some ART medications can still influence cardiovascular risk. For example, PIs are associated with increased triglyceride levels and greater plaque formation.
 
Despite these risks, ART remains crucial in reducing the pro-inflammatory effects of HIV. Studies like the SMART and START trials have shown that continuous ART use reduces the risk of AIDS-related complications and helps lower cardiovascular risk.
 
Metabolic Challenges in HIV
Metabolic syndrome, which includes conditions such as high blood pressure, abnormal cholesterol levels, and insulin resistance, is more prevalent in PLWH than in the general population. These conditions further exacerbate the risk of CVD. According to the study, untreated HIV can lead to significant reductions in HDL (good cholesterol) and increases in triglycerides, further promoting plaque formation in the arteries.
 
Interestingly, changes in body composition are also common in HIV patients, particularly those on ART. An increase in visceral fat, particularly around the abdomen, is commonly observed. This fat accumulation is associated with a higher risk of CVD and is exacerbated by certain ART medications.
 
The Impact of Co-Infections
Co-infections with other viruses, such as Hepatitis C and B, further complicate the cardiovascular health of PLWH. These co-infections contribute to chronic inflammation and endothelial dysfunction, amplifying the risks associated with atherosclerosis. In particular, co-infection with Hepatitis C has been linked to higher levels of pro-inflammatory markers, worsening the overall cardiovascular risk profile in HIV patients.
 
Current and Emerging Treatments for Cardiovascular Risk in HIV
Management of cardiovascular risk in PLWH involves both lifestyle interventions and pharmacological treatments. Statins and aspirin are widely recommended for reducing cardiovascular-related morbidity and mortality in PLWH, just as they are in the general population. However, the study notes that the prescription of these medications remains suboptimal in HIV-positive populations.
 
Statins, in particular, are recommended for PLWH with a history of vascular disease or those at high cardiovascular risk, regardless of their cholesterol levels. For those who cannot tolerate statins or fail to meet LDL cholesterol targets, PCSK9 inhibitors, a newer class of cholesterol-lowering drugs, have shown promise.
 
The study also highlights the importance of early detection and monitoring of cardiovascular risk in PLWH. Regular screening for lipid abnormalities, blood pressure, and inflammation markers is crucial in preventing cardiovascular events.
 
Conclusion
The relationship between HIV and cardiovascular disease is complex, involving a myriad of factors ranging from the direct effects of the virus to the side effects of antiretroviral therapy. Chronic inflammation and immune activation are central to this process, contributing to the development of atherosclerosis and increasing the risk of heart attacks and strokes.
 
To effectively manage cardiovascular risk in PLWH, a multidisciplinary approach is essential. This includes regular monitoring of cardiovascular health, lifestyle modifications, and the use of medications like statins and PCSK9 inhibitors. Additionally, newer ART regimens with fewer metabolic side effects should be prioritized to minimize cardiovascular risk.
 
The study findings were published in the peer-reviewed journal: Infectious Disease Reports.
https://www.mdpi.com/2036-7449/16/5/66
 
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