Antiplatelet Therapy in HIV
Condition: HIV; Cardiovascular Diseases; Inflammation
MeSH terms: Cardiovascular Diseases; Inflammation
Study type: Interventional
Phase: Phase 2

Summary: 
      The proposed study will add to the growing understanding of platelet activity and platelet
      inhibition in subjects with HIV. It will examine the relationship between platelet activity
      and its inhibition by antiplatelet therapy (aspirin monotherapy and clopidogrel monotherapy)
      in this high-risk cohort. Furthermore, it will provide important data on the mechanism of
      platelet activity and its inhibition using biomarkers of platelet activity, inflammation,
      immune activity and endothelial function and genetic expression profiling.
    

Detailed description: 
      There is substantial evidence that the risk of serious non-AIDS conditions, such as
      cardiovascular disease, kidney disease, liver disease, and non-AIDS-defining malignancies, is
      increased in persons with HIV infection as compared to the general population. HIV-induced
      activation of inflammatory and coagulation pathways have been implicated in this increased
      risk. However, causative mechanisms linking HIV, inflammation, and increased risk of non-AIDS
      diseases are poorly described. The investigators are interested in studying the link between
      HIV induced inflammation and cardiovascular disease. Inflammation mediates many aspects of
      disease pathogenesis in atherosclerosis, involving diverse cell types and mediating signals.
      Specifically, platelets have been implicated in atherosclerosis because of their
      pro-inflammatory and thrombogenic effects. Moreover, clinical studies have demonstrated the
      importance of platelet activity in coronary artery atherosclerosis and thrombosis. Whereas
      there is a great understanding of the pathogenesis of cardiac disease, there is a wide
      knowledge gap in the understanding of mechanisms of cardiovascular disease in patients with
      HIV.

      A recent study by the investigators demonstrated that platelet activity is heightened in
      subjects with HIV. Following 1-week of low-dose aspirin, platelet activity was inhibited. A
      surprising finding of this study demonstrated that antiplatelet therapy with 1 week of
      aspirin (325mg dose x1 day followed by 81mg daily) improved immune activity in subjects with
      HIV. The current study is being performed to replicate those findings when compared with a
      control group. Moreover, it remains unknown if the finding was specific to aspirin or whether
      the results were attributed to the antiplatelet effect of the drug. Clopidogrel is another
      antiplatelet therapy that targets the P2Y12 receptor (a different mechanism than aspirin)
      that has been shown to lower the risk of cardiovascular events in various clinical settings.
      The doses of aspirin and clopidogrel the investigators will be employing have been tested in
      hundreds of studies with well-known benefits and risks. The investigators believe that
      understanding the mechanistic role of platelet inhibitors in the setting of HIV will help
      uncover a new strategic pathway of HIV pathogenesis. Also, subjects with HIV are at increased
      risk for cardiovascular events and understanding the platelet inhibition of aspirin and
      clopidogrel will help establish better designs for future trials aimed at preventing these
      events in HIV infected persons.

      The investigators have demonstrated that platelet activation is increased in HIV infection
      and can be attenuated by low-dose aspirin in a non-randomized study without a control group.
      Therefore, the Specific Aims of the study to be established are as follows:

        -  The effect of aspirin versus control on markers of platelet activity, inflammation,
           immune activity, and endothelial function.

        -  The effect of Clopidogrel versus control on markers of platelet activity, inflammation,
           immune activity, and endothelial function.
    

Intervention name(s): Aspirin; Clopidogrel
Intervention type(s): Drug; Drug
Intervention MeSH terms: Aspirin; Clopidogrel
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Prevention