Tick Saliva Molecule Blocks Mechanism Behind Increased Cardiovascular Risks Associated with HIV
NIH study sheds light on the mechanism behind increased cardiovascular risks for those living with HIV.
Now that individuals with HIV are living longer lives thanks to antiretroviral therapy (ART), they are also at increased risk for ischemic stroke, heart failure, and cardiovascular disease (CVD). Although the associated risk of these conditions in the HIV-positive patient population is known, the underlying mechanism driving the risk has not been clear, until now.
New research from the National Institutes of Health (NIH) sheds light on the mechanism behind cardiovascular risks by taking a closer look at how “chronic inflammation and persistent immune activation associated with HIV” drives risk in infected individuals, according to a recent press release.
Several past studies have shown that HIV-positive individuals are 50% to 75% more likely to experience acute myocardial infarction (AMI) than those without the virus, even when infection is well-controlled by ART.
In the study, published in the journal Science Translational Medicine, the researchers found that monocytes in HIV-positive individuals proliferate, “expressing proteins and triggering inflammation and abnormal blood clotting.” Furthermore, the researchers found that an experimental drug was capable of blocking this from happening in nonhuman primate models.
The team, led by Irini Sereti, MD, of the Laboratory of Immunoregulation at the National Institute of Allergy and Infectious Diseases (NIAID), along with Ivona Pandrea, MD, PhD, from the University of Pittsburgh, assessed blood samples collected from HIV-positive individuals. They found high levels of monocytes that expressed elevated levels of tissue factor (TF) in the samples; TF is a protein associated with inflammation and blood clotting. The researchers were surprised to find that even if the infection was well-controlled with the help of ART, the elevated levels of monocytes were still present.
Researchers then exposed the samples to “an experimental anticoagulant” called Ixolaris, which is derived from tick saliva and has been known to “block the cellular pathway that activates TF.” As a result, “TF activity was shut off” in the monocytes without affecting the normal functionality of the cell.
They noted the same elevated levels of monocytes expressing TF in nonhuman primates that were infected with the monkey equivalent of HIV: SIV. Monkeys treated with the anticoagulant possessed “lower levels of biomarkers that predict abnormal blood clotting and immune activation,” compared with previous data collected on SIV-infected monkeys.
The researchers suggest that targeting the TF pathway may result in reduced cardiovascular risk factors. Ixolaris has yet to be tested in humans for its safety or efficacy in the prevention of abnormal blood clotting. However, the study suggests that targeting this pathway "may slow the inflammation and clortting processes" that put HIV-positive individuals at increased risk of developing cardiovascular issues.