Effects of tipranavir, darunavir, and ritonavir on platelet function, coagulation, and fibrinolysis in healthy volunteers

Curr HIV Res. 2011 Jun;9(4):237-46. doi: 10.2174/157016211796320306.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Coagulation / drug effects
  • Blood Coagulation Factors / drug effects
  • Darunavir
  • Drug Therapy, Combination
  • Female
  • Fibrinolysis / drug effects*
  • HIV Protease Inhibitors / pharmacology*
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation / drug effects*
  • Prospective Studies
  • Pyridines / pharmacology*
  • Pyrones / pharmacology*
  • Ritonavir / pharmacology*
  • Sulfonamides / pharmacology*


  • Blood Coagulation Factors
  • HIV Protease Inhibitors
  • Pyridines
  • Pyrones
  • Sulfonamides
  • Ritonavir
  • Darunavir
  • tipranavir