Human recombinant DNA-derived antihaemophilic factor (factor VIII) in the treatment of haemophilia A: conclusions of a 5-year study of home therapy

Fifty-eight previously treated haemophilic subjects were treated exclusively with the recombinant FVIII (rFVIII-KOGENATE®) produced by Bayer Corporation (Berkeley, CA) in an international multicentre prospective study of more than 5 years duration. Fifty-four of the 58 had severe haemophilia (< 2% FVIII) and four had moderate haemophilia (2–5% FVIII); 23/58 (40%) were seropositive for HIV, while 35/58 (60%) were HIV seronegative. Patients were monitored for safety and efficacy over a median period of 4.7 years (range 0.9–5.9 years) and received 17 922 infusions totalling 25.7 million units of rFVIII. Of 7107 bleeding episodes reported in home diaries, 5831 (82%) required only one treatment with rVIII. Twenty-five invasive surgical procedures in 17 patients, including eight joint replacements, were successfully accomplished and 13 serious bleeding episodes in eight patients were successfully treated. FVIII recovery performed on 885 occasions using 39 different lots of rFVIII showed mean incremental recovery of 2.48% IU^?1 kg^?1 (± 0.64). Adverse events were associated with 42 infusions (0.2%); none caused discontinuation of therapy. Immunological parameters remained stable in HIV-seronegative subjects treated with rFVIII; a small decrease in CD4 counts was noted in HIV-seropositive individuals (mean ? 37.2 cells mm–3 yr^?1). No de novo formation of inhibitors to FVIII was noted; and no clinical allergic reactions occurred to murine or hamster proteins. These conclusions from the longest monitored safety study ever performed for a haemophilia treatment product (with more than 5 years of observation) confirm previous interim study reports that rFVIII is well tolerated over the long-term, has biological activity comparable to that of plasma-derived FVIII, and is safe and efficacious for the treatment of haemophilia A.     

Liver failure and mortality in HIV-positive haemophiliacs: FOURTEEN-YEAR EXPERIENCE AND LITERATURE REVIEW

Progression to clinical liver failure has been observed in hepatitis C (HCV)-infected, HIV-seropositive haemophiliacs. We studied the records of 176 haemophiliacs who were infected with HIV and/or HCV seen between 1980 and 1993. Thirty-two of 113 (28%) HIV-seropositive patients died during the study period. Ten of these patients died of liver failure, representing 31% of all mortality. An additional four HIV-seropositive patients who died of other causes had end-stage liver disease. Clinical liver failure occurred in 12% of the HIV-infected cohort. None of the HIV-seronegative, HCV-infected patients suffered from liver failure. Among HIV-infected patients, liver failure was associated with advanced age and decreased CD4 counts. Severe, sporadic ALT elevations were associated with liver failure; persistent transaminase elevations were associated with mortality. We conclude that HIV infection enhances progression of HCV infection to clinical liver failure, and that liver failure is a major cause of mortality in HIV-positive haemophiliacs.