Researchers have uncovered a new pathway by which HIV leads to the chronic inflammation and immune activation associated with an increased risk of cardiovascular disease. Using an experimental drug based on an anticlotting factor in tick saliva, the scientists were able to block this pathway in primates. Such success indicates that a drug may one day be developed that helps mitigate the increased risk of heart disease associated with HIV.
Even when taking a successful antiretroviral (ARV) regimen, people with HIV have up to a two-fold increased risk of cardiovascular disease, including heart attack and stroke, compared with HIV-negative individuals. Researchers believe that the chronic inflammatory state and the persistent activation of the immune system to which the virus gives rise is likely a major driver of this increased risk.
A major clinical trial called REPRIEVE is currently investigating whether a drug from the cholesterol-lowering class called statins may mitigate this risk and provide other health benefits among people with HIV who would not otherwise qualify for a statin.
Publishing their findings in Science Translational Medicine, National Institute of Allergy and Infectious Diseases (NIAID) scientists studied blood samples from people with HIV. They discovered elevated levels of immune cells known as monocytes that expressed high levels of a protein known as a tissue factor, which is linked with blood clotting and processes that give rise to inflammation.
The scientists further discovered that the level of such monocytes remained high regardless of whether the HIV-positive people who provided the blood samples had a fully suppressed virus thanks to ARV treatment.
Next, the researchers exposed the blood samples to an experimental drug called lxolaris, which is based on an anticlotting factor found in tick saliva. Previous research has shown that lxolaris blocks the cellular pathway that activates the tissue factor protein. The investigators found that the drug indeed shut off that particular protein in monocytes and did not otherwise affect normal cell function.
Studying monkeys infected with SIV, HIV’s simian cousin, the investigators found that the animals also had high levels of tissue-factor-expressing monocyte cells. So they treated five monkeys with lxolaris and found that this lowered levels of biomarkers that predict abnormal blood clotting and immune activation.
This finding signifies that by targeting the tissue factor pathway, lxolaris may lower some risk factors for cardiovascular disease among people with HIV. The drug has not yet been tested in humans, however, so considerable research would be needed to determine whether lxolaris may slow the inflammation and clotting processes that raise the risk of cardiovascular disease among people with HIV.
To read a POZ feature article about cardiovascular risk among people with HIV and whether they should take a statin, click here. And for more information on how individuals living with the virus can lower their risk of heart disease, click here. Lastly, click here for an article about chronic inflammation and its significance for people with HIV.
For information on joining the REPRIEVE trial, click here.
To read a press release about the study, click here.