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Effects of Tipranavir, Darunavir, and Ritonavir on Platelet Function, Coagulation, and Fibrinolysis in Healthy Volunteers

[ Vol. 9 , Issue. 4 ]

Author(s):

Jens J. Kort, Stella Aslanyan, Joseph Scherer, John P. Sabo, Veronika Kohlbrenner and Patrick Robinson   Pages 237 - 246 ( 10 )

Abstract:


The use of HIV protease inhibitors (PIs) as part of antiretroviral therapy in the treatment of HIV-1 infection may be associated with an increased risk of bleeding. This prospective, randomized, open-label trial in healthy volunteers compared the effects of tipranavir/ritonavir (TPV/r), darunavir/ritonavir (DRV/r), and ritonavir (RTV) alone on platelet aggregation after a single dose and at steady-state concentrations. Subjects were selected on the basis of normal platelet aggregation and arachidonic acid (AA)-induced platelet aggregation inhibition after administration of a single 325-mg dose of aspirin. All 3 PI therapies were administered twice daily for 10 days.

In some but not all subjects, TPV/r inhibited AA-induced platelet aggregation and prolonged PFA-100® closure time with collagen-epinephrine cartridge, which was of lesser magnitude and consistency compared with aspirin, but greater when compared to DRV/r and RTV. At least 2 subjects in each treatment arm showed complete inhibition of AA-induced platelet aggregation on treatment, and the magnitude of change in all platelet-function tests did not correlate with PI plasma concentrations. Effects of TPV/r on platelet aggregation were reversed 24 hours after the last TPV/r dose. None of the PI treatments tested were associated with increases in bleeding time, decreases in plasma coagulation factors, or increase in fibrinolysis. There was large inter-patient variability in antiplatelet effect for all PI treatments, ranging from no effect to complete inhibition of AA-induced platelet aggregation.

Keywords:

Aggregation, aspirin, bleeding time, coagulation, fibrinolysis, platelet, protease inhibitor, HIV infection, tuberculosis, AIDS defining illness, AIDS, antiretroviral therapy, HAART, CoRIS, Mycobacterium tuberculosis, HIV-1-Infected Patients, CD4+, Short-Term Clinical Outcome

Affiliation:

Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA.



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