Protease inhibitor therapy and bleeding.

Shortly after the introduction of protease inhibitor drugs (PIs) for the treatment of human immunodeficiency virus infection an association between these drugs and an increased bleeding tendency in patients with hereditary bleeding disorders was observed. Not only do patients experience an increased bleed frequency in usual sites, but bleeds can also occur in unusual places such as the finger joints. Mucus membrane bleeding and haematuria are also common. Ritonavir appears to be associated with the highest risk of bleeding followed by indinavir. As yet there has not been enough experience with the newer PIs to assess fully their potential to induce increased bleeding, although nelfinavir seems to pose less of a risk than the original PIs. PI-associated bleeds tend to be more resistant to factor concentrate treatment and periods of prophylaxis may be required in individuals with frequent persistent bleeds. Patients continuing on PI therapy tend to develop a tolerance to this adverse effect with time. The mechanism of the bleeding tendency has not been elucidated. There is no consistent evidence of a disturbance of coagulation, fibrinolysis or platelet function which raises the possibility that PIs may exert a direct local effect on blood vessels. It is very important that this class-specific side-effect is recognized and understood by both treaters and patients.