Three-year randomised study of high-purity or intermediate-purity factor VIII concentrates in symptom-free HIV-seropositive haemophiliacs: effects on immune status

Abstract

Summary The availability of monoclonal-antibody-purified factor VIII (FVIII) concentrates allows us to test the hypothesis, based on in vitro observations, that their use in HIV seropositive haemophiliacs would result in a difference in the rate of deterioration of immune function. We designed a multicentre, prospective, randomised, controlled study of symptom-free HIV-infected patients with haemophilia A who were assigned to receive either an intermediate-purity or monoclonal-antibody-purified product. All had CD4 lymphocyte counts of 100-600/μL, were negative for hepatitis B surface antigen, had not received any antiretroviral or immunomodulating drugs before study entry, and had previously received replacement therapy with intermediate purity FVIII concentates. Use of antiretroviral therapy was permitted. 60 patients were recruited and 30 were assigned to each group. 35 completed the 3 year study, 20 in the monoclonal arm and 15 in the intermediate-purity arm. Among those completing the study, there were no differences between the two groups in the occurrence of AIDS-defining diagnoses (1 in each group). There were, however, striking and significant differences in terms of changes in absolute CD4 counts. The group receiving monoclonal-antibody-purified concentrates had essentially stable counts while a significant drop was observed in the group receiving intermediate-purity FVIII. These differences were independent of the use of antiretroviral therapy. These observations support the use of high-purity concentrates in the treatment of symptom-free HIV-positive patients with haemophilia A, and they should be taken into account along with cost, by doctors making therapeutic decisions.