P11. Changes in platelet aggregation and coagulation in HIV-1 patients switching to or from abacavir: Tenofovir Abacavir Platelet Activation Study (TAPAS)

Frederikke Falkencrone Rönsholt Md Phd1, Marie Helleberg Md Phd Dmsc1, Pär Ingemar Johansson Professor Md Dmsc Mpa2, Judith Haismann Md1, Sisse Rye Ostrowski Md Phd Dmsc2, Jan Gerstoft Professor Md Dmsc1.
Affiliates: 1Department of Infectious Diseases 8632, Copenhagen University Hospital Rigshospitalet, Denmark 2Section for Transfusion Medicine, Capital Region Blood Bank 2032, Copenhagen University Hospital Rigshospitalet, Denmark

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Background
Some studies have reported an association between abacavir and an increased risk of cardiovascular events. TAPAS aimed to determine changes in platelet aggregation, functional coagulation and markers of coagulation after switching to or from abacavir as part of combination antiretroviral therapy (cART).

Methods
TAPAS is an investigator initiated, open labeled, cross over study. Participants receiving cART containing abacavir/lamivudine switched treatment to a regimen containing tenofovir/emtricitabin (AT group) and vice versa (TA group). The third cART drug remained unchanged. Blood samples were drawn before switching and 85-90 days after therapy change. Platelet aggregation was analysed by impedance aggregometry with the following agonists: Adenosinediphosphate (ADP), arachidonic acid (ASPI), thrombin receptor agonist peptide (TRAP) and ristocetin in high (RISTOhi) and low (RISTOlow) concentrations. Functional coagulation was assessed by thromboelastography (TEG) using the variables reaction time, angle, maximal amplitude, time to maximal amplitude, lysis after 30 minutes, and clot lysis time. Further, platelet count, coagulation factors II-VII-X (CF), fibrinogen and antithrombin III (AT3) were measured.

Results
We included 55 male individuals of whom 19 and 24 completed the study in the AT and the TA group, respectively.
The platelet aggregometry showed no differences between the groups in absolute change in platelet reactivity with either of the examined agonists.
Likewise, TEG showed no differences between the groups in absolute change in any of the given variables.
Changes in platelet counts, fibrinogen levels and AT3 levels were also similar between groups. In the TA group, CF increased median 0.13 units/L (IQR 0.04-0.20), whereas a decrease of median -0.07 units/L (IQR -0.13 – -0.04) was observed in the AT group (P<0.0001).

Conclusions
Switching between abacavir and tenofovir based cART regimens did not alter platelet reactivity, however, switching from tenofovir to abacavir resulted in an increase in coagulation factors II-VII-X. It remains unclear whether these changes have any clinical significance.

P11-frederikke falkencone