PCSK9 Levels Raised in Asymptomatic HIV Patients

MARCH 08, 2018
Kevin Kunzmann
Markella V. Zanni, MDMarkella V. Zanni, MD
Levels of proprotein convertase sutilisin/kexin 9 (PCSK9), the enzyme encoded on chromosome 1, are elevated in asymptomatic patients with HIV — possibly giving researchers another resource by which to diagnose HIV in patients who may not be indicative of the virus.

But before that resource is fully understood, more must be uncovered on the potential benefits of PCSK9 inhibition for patients with HIV.

In a study presented at the 25th Conference on Retroviruses and Opportunistic Infections (CROI) in Boston, MA this week, locally-based researchers reported that patients with HIV who do not show symptoms have elevated PCSK9 levels, which are related to systemic markers of monocyte activation in patients.

The enzyme, noted for mediating homeostasis of low density lipoprotein cholesterol (LDL-C), is also capable of a role in immune reactivity and atherogenesis — it is released into circulation by diverse cell types once they have been stimulated by pro-inflammatory milieu.

Though PCSK9 levels are commonly associated with risk of major adverse cardiovascular events, it could also release pro-inflammatory responses in monocytes/ macrophages, with relevance to immune-mediated atherogenesis.

Led by Markella V. Zanni, MD, of the Massachusetts Department of Public Health in Boston, researchers sought to answer whether asymptomatic patients with HIV would show elevated PCSK9 levels in relation to systemic monocyte activation markers and/or subclinical coronary atherosclerotic plaque parameters, versus the levels of a person without HIV.

Patients with HIV are known to have increased levels of systemic immune activation, as well as increased subclinical coronary atherosclerotic plaque burden.

Researchers assessed the levels of 218 participants (149 HIV infected; 69 non-HIV infected) through the enzyme-linked immunosorbent assay (ELISA) test. They found that the mean PCSK9 levels were more elevated in patients with HIV versus non-matched subjects (332 ng mL [272, 412] vs. 304 ng/mL [257,375]; P = 0.047).

There was also a significant positive association found between PCSK9 levels and systemic monocyte activation markers including sCD14 (rho = 0.22; P = 0.009) and sCD163 (rho = 0.23; P = 0.006). However, there was no found relation between PCSK9 levels and subclinical coronary atherosclerotic plaque parameters in either patient group.

Researchers concluded that because PCSK9 inhibition lead to significant cardiovascular disease prevention, more analysis will be needed to distinguish whether PCSK9 inhibition may reduce immune activation and coronary plaque burden in the HIV population.

Further research is also needed to determine PCSK9’s effects on immune activation and atherogenesis in patients with HIV.

The study, “PCSK9 Levels in Relation to Immune Activation and Subclinical Coronary Plaque in HIV,” was published online on the CROI meeting website.

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