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

TitleA Randomized Placebo Controlled Trial of Aspirin Effects on Immune Activation in Chronically Human Immunodeficiency Virus-Infected Adults on Virologically Suppressive Antiretroviral Therapy.
Publication TypeJournal Article
Year of Publication2017
AuthorsO'Brien MP, Hunt PW, Kitch DW, Klingman K, Stein JH, Funderburg NT, Berger JS, Tebas P, Clagett B, Moisi D, Utay NS, Aweeka F, Aberg JA
JournalOpen Forum Infect Dis
Volume4
Issue1
Paginationofw278
Date Published2017 Winter
ISSN2328-8957
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 B, 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.

DOI10.1093/ofid/ofw278
Alternate JournalOpen Forum Infect Dis
PubMed ID28480270
PubMed Central IDPMC5414028
Grant ListUM1 AI069494 / AI / NIAID NIH HHS / United States
UM1 AI069471 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI069496 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States
UM1 AI069532 / AI / NIAID NIH HHS / United States
K08 AI093153 / AI / NIAID NIH HHS / United States
R56 HL127995 / HL / NHLBI NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States