Background: Mechanisms for increased cardiovascular risk in HIV-1-infected adults are incompletely understood, but platelet activation and immune activation leading to a prothrombotic state have been proposed as significant contributors. Aspirin has antiplatelet and immunomodulatory properties. We explored whether 1 week of low-dose aspirin attenuates platelet activation and immune activation in HIV-1-infected and virologically suppressed adults on antiretroviral therapy.
Methods: Platelet activation and immune activation were measured in HIV-1-infected subjects virologically suppressed on antiretroviral therapy and controls before and after 1 week of low-dose aspirin.
Results: Compared with control subjects, HIV-1-infected subjects had increased platelet activation, as measured by spontaneous platelet aggregation and aggregation in response to adenosine diphosphate, collagen, and arachidonic acid. After aspirin therapy, percent aggregation decreased similarly in both HIV-1-infected and control subjects to all platelet agonists tested except aggregation in response to arachidonic acid, which remained elevated in the HIV-1-infected group. HIV-1-infected subjects exhibited increased markers of T-cell activation (CD38 and HLA-DR) and monocyte activation (sCD14), which decreased after 1 week of aspirin therapy. Moreover, leukocyte responses to Toll-like receptor stimulation were enhanced after 1 week of aspirin therapy. In vitro studies showed that HIV-1 plasma could activate healthy platelets, which in turn activated monocytes, implicating a direct role for activated platelets in immune activation.
Conclusions: Our data demonstrate that heightened platelet activation and immune activation in treated HIV-1 disease are attenuated by 1 week of aspirin therapy. Aspirin should be further studied for its antithrombotic and immunomodulatory benefits in treated HIV-1 disease.
*Division of Infectious Diseases and Immunology, Cancer Institute, New York University, School of Medicine, New York, NY;
†Bellevue Hospital Center, New York City Health and Hospital Corporation, New York, NY;
‡Divisions of Cardiology and Hematology, New York University, School of Medicine, New York, NY;
§Divisions of Hematology, Oncology, and Pathology, Department of Pediatrics, New York University, School of Medicine, New York, NY;
‖Division of Infectious Diseases and Immunology, New York University, School of Medicine, New York, NY; and
¶Divisions of Pathology and Dermatology, Cancer Institute, New York University, School of Medicine, New York, NY.
Correspondence to: Meagan O’Brien, MD, NYU Langone Medical Center, 522 First Avenue, SML 1307, New York, NY 10016 (e-mail: meagan.o’firstname.lastname@example.org).
Supported by the Center for AIDS Research pilot project grant P30 AI027742, in part by the National Center for the Advancement of Translational Science (NCATS) Grant No. UL1 TR000038 (M.O., J.S.B.), the the National Institutes of Health National Institute of Allergy and Infectious Diseases Grant No. 5 U01 AI069532 (J.A.A., K.C.), the Grunebaum AIDS research scholarship (M.O.), and by an American Heart Association Fellow to Faculty Award (0775074N) and a Doris Duke Clinical Scientist Development Award (2010055) (J.S.B.).
The authors have no conflicts of interest to disclose.
M.O. designed the study and performed experiments, analyzed and interpreted data, and drafted and revised the article. G.G., L.H., M.M., E.M., V.V. and M.A.N. collected data and performed selected experiments. K.C. contributed to experimental design and collected data. J.A.A. and N.B. contributed to experimental design and revised the article. J.S.B. designed the study, analyzed and interpreted data, and drafted and revised the article.
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Presented, in part, at the XIX International AIDS Conference, July 2012, Washington, DC.
Received November 26, 2012
Accepted January 28, 2013