A Randomized Placebo Controlled Trial of Aspirin Effects on Immune Activation in Chronically Human Immunodeficiency Virus-Infected Adults on Virologically Suppressive Antiretroviral Therapy.

Abstract

BACKGROUND:

Immune activation persists despite suppressive antiretroviral therapy (ART) in human immunodeficiency virus (HIV) infection and predicts non-Acquired Immune Deficiency Syndrome (AIDS) comorbidities including cardiovascular disease. Activated platelets play a key role in atherothrombosis and inflammation, and platelets are hyperactivated in chronic HIV infection. Aspirin is a potent inhibitor of platelet activation through the cyclooxygenase-1 (COX-1) pathway. We hypothesized that platelet activation contributes to immune activation and that aspirin would reduce immune activation and improve endothelial function in ART-suppressed HIV-infected individuals.

METHODS:

In this prospective, double-blind, randomized, placebo-controlled 3-arm trial of 121 HIV-infected participants on suppressive ART for >48 weeks, we evaluated the effects of 12 weeks of daily aspirin 100 mg, aspirin 300 mg, or placebo on soluble and cellular immune activation markers, flow-mediated dilation (FMD) of the brachial artery, and serum thromboxane B2, a direct readout of platelet COX-1 inhibition.

RESULTS:

The 300-mg and 100-mg aspirin arms did not differ from placebo in effects on soluble CD14, interleukin (IL)-6, soluble CD163, D-dimer, T-cell or monocyte activation, or the other immunologic endpoints measured. Endothelial function, as measured by FMD, also was not significantly changed when comparing the 300-mg and 100-mg aspirin arms to placebo.

CONCLUSIONS:

Aspirin treatment for 12 weeks does not have a major impact on soluble CD14, IL-6, soluble CD163, D-dimer, T-cell or monocyte activation, or FMD, suggesting that inhibition of COX-1-mediated platelet activation does not significantly improve HIV-related immune activation and endothelial dysfunction. Although future studies are needed to further identify the causes and consequences of platelet activation in ART-treated HIV infection, interventions other than COX-1 inhibition will need to be explored to directly reduce immune activation in treated HIV infection.

• Authors: Meagan P O'Brien, Peter W Hunt, Douglas W Kitch, Karin Klingman, James H Stein, Nicholas T Funderburg, Jeffrey S Berger, Pablo Tebas, Brian Clagett, Daniela Moisi, Netanya S Utay, Fran Aweeka, Judith A Aberg
• Journal: Open forum infectious diseases (Open Forum Infect Dis) Vol. 4 Issue 1 Pg. ofw278 ( 2017) ISSN: 2328-8957 [Print] United States
• PMID: 28480270 (Publication Type: Journal Article)
• Copyright: © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America.