HIV treatments have made enormous strides in recent decades, but patients—even those on antiretroviral drugs—have a higher risk of developing heart disease. An experimental drug based on tick saliva may be the key to reducing the inflammation that causes these complications.
People with HIV have an elevated risk of neurological and cardiovascular complications because they have higher levels of monocytes that express the “tissue factor” (TF) protein. This protein triggers blood clotting and inflammation even in people whose infection is well-controlled by antiretrovirals, researchers from the NIH and the University of Pittsburgh found.
They confirmed the role of monocytes and the TF protein by looking at two species of monkeys with SIV, the primate version of HIV. Pigtail macaques have TF-expressing monocytes and develop heart disease after SIV infection, while African green monkeys have monocytes that do not express TF and tend not to develop heart disease after SIV infection.
The researchers found that the experimental drug Ixolaris, which is derived from the saliva of the deer tick, successfully tamped down on inflammation in macaques with SIV. They also tested it in blood samples from healthy people as well as from two groups of people with HIV—those who were on antiretroviral medication and those who weren’t. The drug blocked the activity of the TF protein, they found. The findings are published in Science Translational Medicine.
In addition to receiving antiretroviral treatment, patients may be treated for complications and conditions associated with HIV infection. But the search for a permanent cure, or at least longer-acting antiretrovirals, is ongoing. New approaches include using CRISPR to cut HIV out of HIV-positive cells, targeting reservoirs of HIV that persist in macrophages and developing a vaccine based on an HIV-fighting antibody that cows naturally produce.
Even if those efforts succeed, there will still be a need for therapies to treat the consequences of HIV. "People are living long, fruitful lives with HIV thanks to tremendous strides in antiviral treatment regimens, however those lives are being cut short due to perplexingly high rates of heart disease," said co-senior author Ivona Pandrea, M.D., Ph.D., a professor of pathology at the University of Pittsburgh’s Center for Vaccine Research, in a statement. "By uncovering one of the cellular mechanisms driving the heart disease, we can look for medications—such as Ixolaris—that specifically target and disrupt that mechanism."
Ixolaris has been used to treat blood clots in animals, but has not yet been tested in humans. More tests are required to assess its safety and any interactions it may have with other drugs used to treat HIV patients, the researchers said.
"This treatment has the potential to improve the clinical management of HIV-infected patients and help them to live longer, healthier lives with HIV," Pandrea said. "That, and other therapies that may arise from targeting the inflammation pathway we discovered, are exciting avenues for future research."