Abstract
INTRODUCTION: People with HIV currently face a tenfold higher risk of developing cardiovascular disease (CVD) than those without HIV. Studies have shown various off-target effects of antiretroviral treatment (ART) on the cardiovascular system, but little is known about the effects of currently used integrase strand transfer inhibitors (INSTIs) on platelets. Platelet activation is associated with increased CVD, thrombus formation, and release of proinflammatory mediators, so exploring platelet effects from currently prescribed ART may contribute to the understanding of CVD etiopathogenesis in people with HIV. METHODS: We aimed to identify potential effects of INSTIs on platelet aggregation and activation markers from individuals without HIV after in vitro treatment with clinically relevant drug concentrations. We used bictegravir (BIC) and dolutegravir (DTG) individually or in the therapeutic drug combinations BIC/emtricitabine (FTC)/tenofovir alafenamide fumarate (TAF) or DTG/lamivudine (3TC). Additionally, we conducted a pilot study to compare platelet activity profiles from people with HIV on BIC/FTC/TAF and DTG/3TC. RESULTS: Changes to in vitro platelet aggregation responses upon exposure to different INSTIs were observed both upon individual drug application and when using therapeutic combinations. However, these effects were not reflected in flow-cytometric evaluation of platelet degranulation. A pilot study in eight people with HIV and eight without HIV revealed no significant effects but established protocols for future patient studies. CONCLUSION: There is currently no consistent evidence of an effect of INSTIs on platelet activation. Further study is warranted, focusing on models with more pathophysiological relevance, including extensive studies in people with HIV.