Could this enzyme reduce the risks of HIV medication?

Antiviral medications used to control HIV and prevent its progression to AIDS improve the health and increase survival for people with HIV—but their use has been linked to the development of cardiovascular disease.

Now, researchers have identified an enzyme that may reduce the risk.

“The use of antivirals in HIV patients is very important to control the virus, suppress symptoms, and improve quality of life,” says William Durante, professor of medical pharmacology and physiology at the University of Missouri School of Medicine and author of a new study published in Free Radical Biology and Medicine.

“However, antivirals also are linked to the development of metabolic disorders such as diabetes and obesity, and they are known to increase the risk of cardiovascular disease. Our study focused on protease inhibitors, a very common antiviral used to treat HIV.”

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Protease inhibitors disrupt HIV’s ability to replicate and infect cells. However, they also cause endothelial cell malfunction, which can lead to cardiovascular disease.

“Endothelial cells make up the inner lining of blood vessels and are essential to vascular health,” Durante says. “When protease inhibitors are used to treat HIV, endothelial cell function is compromised. The cells’ natural tendency to promote blood flow through the vessel is lost and they also become inflamed. These issues lead to plaque build-up within arteries and, ultimately, cardiovascular disease.”

Durante knew from previous studies that the enzyme heme oxygenase-1, or HO-1, offers protection against endothelial dysfunction. Using a cell-based model of cultured human endothelial cells, his team was able to increase the amount of the enzyme within the cells.

“Increasing the presence of HO-1 in our model before exposing it to a protease inhibitor allowed the medication to do its job without causing endothelial dysfunction,” Durante says. “HO-1 shows great promise as a defender of endothelial cells in patients being treated for HIV.”

More research is needed to verify that the enzyme will prevent endothelial cell dysfunction with all antiviral medications. However, Durante feels that identifying the enzyme’s role in reducing vascular inflammation with protease inhibitors may one day make it a new option for preventing cardiovascular disease caused by HIV medications.

The National Heart, Lung and Blood Institute of the National Institutes of Health funded the work.