EACS2023: 233 Dolutegravir but not bictegravir exposure increases in vitro platelet aggregation R. Keniyopoullos , A. Khawaja , M. Emerson Imperial College London, National Heart & Lung Institute, London, United Kingdom General data Abstract category: Antiretroviral drugs preclinical Abstract body Purpose: In the modern era of effective antiretroviral therapy (ART), people living with HIV (PLWH) have near-normal life-expectancies but two-times higher occurrence of cardiovascular disease (CVD). Although CVD is associated with some antiretrovirals, little is known about off-target effects of integrase inhibitors (INSTIs) on platelets, key players in CVD risk and progression. Here, we compared how two common INSTIs, bictegravir (BIC) and dolutegravir (DTG), alone or in their ART drug regimens, affect platelet activation, in an effort to better understand CVD risk in PLWH. Method: Platelets were isolated from whole blood obtained by informed consent from HIV-negative donors (60% male, aged 25 ±3 yrs). Platelets were exposed in vitro to clinical plasma C concentrations of antiretrovirals and vehicle (Veh) control for 30min. Platelet activation was assessed in response to collagen [1-30μg/ml], ADP or thrombin receptor activator peptide (TRAP)-6 [1-30μM] by light transmission aggregometry and flow cytometry. Platelet adhesion on collagen under physiological flow was also measured upon INSTI exposure in vitro. Results were analysed using 1- or 2-way ANOVA with a Tukey’s multiple comparison test. Results: DTG treatment induced significantly higher ADP-evoked platelet aggregation compared to BIC (+1.49-fold, p=0.0231) and Veh (+3.6-fold, p=0.0062) at low ADP concentrations. Collagen-activated platelets [3μg/ml] exposed to DTG had +1.94-fold higher percentage aggregation compared to Veh group (p=0.0042). Significant differences were conserved upon combination ART regimen treatments. Conclusions: Our results suggest DTG, alone or in clinical ART combinations, may sensitize platelets to low-level ADP and collagen stimulation. This may indicate DTG, but not BIC, has the potential to increase CVD risk. Further evaluation of platelet activation in vivo and in clinical settings is required to validate our findings. Ultimately, this work may lead to identifying drug regimens with a lower CVD risk, allowing personalised options when treating PLWH. General conditions 1. I confirm that I previewed this abstract and that all information is correct. I accept that the content of this abstract cannot be modified or corrected after the submission deadline and I am aware that it will be published exactly as submitted.: Yes 2. I confirm that the submission of the abstract constitutes my consent to publication (e.g. conference website, programmes, other promotions, etc.). : Yes 3. I herewith confirm that the contact details saved in this system are those of the corresponding author, who will be notified about the status of the abstract. The corresponding author is responsible for informing the other authors about the status of the abstract.: Yes 4. I agree that all data provided may be used (saved, stored, processed, transmitted and deleted) in compliance with the privacy policy to provide the services described.: Yes 1 1 1 1 max 77
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