Protease inhibitor therapy and bleeding

Shortly after the introduction of protease inhibitor drugs (PIs) for the tr eatment of human immunodeficiency virus infection an association between th ese drugs and an increased bleeding tendency in patients with hereditary bl eeding disorders was observed. Not only do patients experience an increased bleed frequency in usual sites, but bleeds can also occur in unusual place s such as the finger joints. Mucus membrane bleeding and haematuria are als o common. Ritonavir appears to be associated with the highest risk of bleed ing 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. P I-associated bleeds tend to be more resistant to factor concentrate treatme nt and periods of prophylaxis may be required in individuals with frequent persistent bleeds. Patients continuing on PI therapy tend to develop a tole rance to this adverse effect with time. The mechanism of the bleeding tende ncy has not been elucidated. There is no consistent evidence of a disturban ce of coagulation, fibrinolysis or platelet function which raises the possi bility that PIs may exert a direct local effect on blood vessels. It is ver y important that this class-specific side-effect is recognized and understo od by both treaters and patients.