Advances in antiretroviral therapy (ART) have resulted in increased survival of the
HIV-infected population; however, this gain in longevity is associated with an increased risk
of cardiovascular disease (CVD). Although ART and traditional risk factors contribute to CVD
in this population, heightened markers of immune activation, inflammation, and coagulation
independently predict morbidity and mortality, suggesting that dysregulation of these systems
plays a significant role in the increased risk of CVD. The investigators believe that
platelet activation is an important driver in HIV-associated immune activation, inflammation,
and coagulation, leading to an increased CVD pathophysiology and risk. Platelets initiate
thrombus formation and also play a key role in vascular inflammation by releasing
pro-inflammatory mediators and cross-talking with other relevant cell types including
leukocytes. Researchers have described platelet hyperreactivity in chronic HIV infection.
Importantly, the investigators demonstrated that one week of anti-platelet therapy (aspirin)
decreased platelet activation and immune activation, with an improved trend in inflammation
and immune parameters. The overall hypothesis is that platelet activation is a major driver
of immune activation, inflammation, and thrombosis in ART-treated HIV infected patients. The
purpose of the proposed proof-of-concept study is to understand the mechanism(s) by which
anti-platelet therapy improves immune and inflammatory parameters in chronic HIV infection.
To test this, the immune modulating and anti-inflammatory effects of 24 weeks of the
anti-platelet drug aspirin as compared to the anti-platelet drug clopidogrel will be
evaluated. Given their different mechanisms of action and inhibitory potency, the
investigators can differentiate whether the potential benefits are mediated via inhibition of
arachidonic acid (aspirin) or inhibition of ADP (clopidogrel) or by the antithrombotic
activity. A secondary goal is to perform multidimensional assays of platelet activity and
thrombogenicity alongside immune activation assays and careful assessments of traditional
risk factors and medication regimens, to understand which parameters are highly associated
with thrombogenicity.