Targeting Platelets in Chronic HIV Infection

Summary

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.

Conditions

• HIV-1 Infection

Interventions

DRUG

Clopidogrel

Clopidogrel 75mg

DRUG

Aspirin

81 mg

DRUG

Placebo

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)

  collaborator NIH

• Icahn School of Medicine at Mount Sinai

  lead OTHER

Principal Investigators

• Meagan O'Brien, MD · Icahn School of Medicine at Mount Sinai

• Juan Badimon, PhD · Icahn School of Medicine at Mount Sinai

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2015-10-31

Primary Completion

2016-11-30

Completion

2016-11-30

FDA Drug

Yes

Countries

• United States

Study Locations