Researchers found a way to block a protein linked
with blood clotting and inflammatory processes using a drug derived from
tick saliva.
August 30, 2017
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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.
Read more articles from POZ, here.
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