The HIV protease inhibitor, ritonavir, dysregulates human platelet function in vitro

• Published in: Thrombosis research Vol. 169; pp. 96 - 104
• Main Authors: Loelius, Shannon G., Lannan, Katie L., Blumberg, Neil, Phipps, Richard P., Spinelli, Sherry L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.09.2018
• Subjects: Adult; Aged; Antiretroviral therapy; Blood Platelets - drug effects; Blood Platelets - pathology; Cardiovascular disease; Cardiovascular Diseases - chemically induced; Female; HIV Infections - drug therapy; HIV Protease Inhibitors - adverse effects; Humans; Male; Middle Aged; Platelet Activation - drug effects; Platelet Aggregation - drug effects; Platelets; Ritonavir - adverse effects; Young Adult; Platelets; Cardiovascular disease; Antiretroviral therapy
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2018.07.003

There are 37 million people globally infected with the Human Immunodeficiency Virus (HIV). People living with HIV can achieve nearly normal lifespans due to the use of antiretroviral drugs (ARVs). However, people living with HIV experience chronic inflammation and increased risk for cardiovascular diseases (CVD) relative to uninfected people. While the cause for this risk is unclear, some ARVs have been associated with CVD, and it is speculated that some ARVs potentiate inflammation in infected individuals. Platelets are a critical link between inflammation and the development and progression of CVD, but the effects of ARVs on platelets are largely understudied. In this study, we examined the effects of ARVs on human platelet function in vitro. Our data show that the ARV ritonavir, a protease inhibitor, severely altered human platelet lipid mediator production (prostaglandin E2 and thromboxane) in both resting and activated platelets. Further characterization revealed that ritonavir altered measures of platelet hemostatic and thrombotic function that included significantly decreased platelet spreading, increased platelet aggregation, and trended toward increased clot strength. These data provide proof-of-principle that ARVs can directly dysregulate human platelets, possibly contributing to inflammation-related comorbidities. These data may provide mechanistic insight into the factors contributing to increased risk of CVD in people living with HIV, and may help guide future development of new HIV agents and ARV regimens that mitigate platelet dysregulation by ARVs. •We studied the direct effects of antiretroviral drugs on human platelets in vitro.•The protease inhibitor ritonavir directly alters platelet function.•Ritonavir increased platelet PGE2 production and decreased TXB2 production.•Ritonavir increased platelet aggregation and spreading.•There is a need for further investigation of direct effects of ARVs on platelets.