SUCCESSFUL USE OF PROTEASE INHIBITORS IN HIV-INFECTED HEMOPHILIA PATIENTS

The haemophilias are a group of inherited haemostatic disorders that r equire regular clotting factor replacement therapy in the severe and m oderately severe subgroups. Prior to the introduction of adequate vira l inactivation methods in 1985, haemophilia patients were at exception ally high risk of contracting blood-borne viruses from factor concentr ates as each batch was derived from the plasma of thousands of donors. As a result, approximately 60% of these patients were infected with H IV between 1979 and 1985, and HIV infection now contributes significan tly to the morbidity and mortality seen in this group. Protease inhibi tors (PIs) have been shown to significantly log reduce viral loads and increase CD4 cell counts in HIV-infected individuals. Recently, there has been concern about their use in HIV-infected haemophilia patients following increased bleeding episodes in some patients during PI ther apy. We prospectively studied the effect of PI therapy in 20 HIV-infec ted haemophilia patients at our centre over a 6-month period, The mean increase in CD4 cell count was 70 x 10(6)/1 and the mean log decrease in viral load was 1.59 over the study period. Gastrointestinal side-e ffects (nausea and vomiting in five, diarrhoea in two) were the most f requent and resulted in discontinuation of the medication in two patie nts. Factor concentrate usage for the group on and off study was simil ar. One severe FVIII patient reported a single episode of an unusual b leed which responded promptly to FVIII concentrate infusion. The signi ficant clinical and laboratory benefits in terms of HIV disease and th e paucity of added bleeding complications suggest that PI therapy shou ld not be withheld from HIV-infected haemophilics. Further prospective studies evaluating the efficacy and possible haemostatic complication s related to these promising inhibitors of the HIV protease are needed .