Loss of high-responder inhibitors in patients with severe hemophilia A and human immunodeficiency virus type 1 infection: a report from the Multi-Center Hemophilia Cohort Study

Abstract

To evaluate the effects of human immunodeficiency virus type 1 (HIV-1) infection on the loss of factor VIII alloantibodies, we identified 77 patients with a history of inhibitors from among a large cohort of HIV-1-infected participants enrolled in a natural history study of HIV-1 infection in hemophilia. Fifty-six patients were high responders with inhibitors titers greater than 5 Bethesda Units (BU) measured on at least one occasion. From May 1985 to December 1989, 13 of the high-responder patients were rechallenged with factor VIII concentrates after several years of treatment with other plasma products. All exhibited excellent hemostasis upon reinstitution of factor VIII. Seven of the 13 patients (11.3-46.3 years of age) were in the advanced stages of HIV-1 infection at the time of rechallenge. Inhibitor titers measured subsequent to the reinstitution of factor VIII were consistently less than 1 BU in five of these seven patients. The remaining six patients (6.1-57.5 years of age) had mild to moderate CD4+ lymphocyte depletion (absolute CD4+ cells: 262-935/mm3) at the time of factor VIII rechallenge. Follow-up inhibitor titers were negative 7-42 months after consistent factor VIII use in these six patients. The lack of anamnestic response to factor VIII in all 13 patients who were rechallenged indicates that HIV-1-infected patients who have a history of high-responder inhibitors frequently benefit from the reintroduction of factor VIII use for the control of bleeding, regardless of their stage of HIV-1 disease