Platelet Transcriptome Profiling in HIV and ATP-Binding Cassette Subfamily C Member 4 (ABCC4) as a Mediator of Platelet Activity.

•Platelet activity and its effector cell properties are increased in persons with virologically suppressed HIV on antiretroviral therapy.•The platelet transcriptome is differentially expressed in participants with HIV compared with healthy individuals.•ABCC4 expression and translation was enhanced in HIV-infected subjects compared with healthy individuals.•ABCC4 is a membrane transporter that plays an important role in regulating several cardiovascular processes, including platelet activation and aggregation.•Platelet ABCC4 inhibition in HIV attenuated platelet activation and platelet effector cell function by regulating cyclic nucleotide homeostasis and the extrusion of platelet proinflammatory mediators.