Effect on lymphocyte subsets of clotting factor therapy in human immunodeficiency virus-1-negative congenital clotting disorders

Patients with hemophilia A without human immunodeficiency virus type 1 (HIV-1) infection have lower CD4⁺ counts and CD4⁺/CD8⁺ ratios than controls. This is usually interpreted as a therapy-induced immunodeficiency. Our data re-examine the effect of therapy on peripheral blood mononuclear cell immunophenotypic subpopulations in all congenital clotting disorders. Since late 1985 we have prospectively observed HIV-1 uninfected persons with all types and severity of disorder. Controls were household members without clotting disorders or HIV-1 infection. Analyses of immunophenotype and treatment included a longitudinal random effects model. Compared with controls, age-adjusted CD4⁺ counts were significantly lower in treated patients (P < .0001) and in patients with all types of clotting disorders who were seldom or never treated (P = .0005). Significantly lower values among both treated and untreated clotting disorder subjects (P < .05) were likewise found for total lymphocytes, several other T-cell subsets, and the CD4⁺/CD8⁺ ratio. For most indexes, including the CD4⁺ count and CD4⁺/CD8⁺ ratio, the type of clotting deficiency was not a significant variable. Comparing persons who had no or minimal therapy with those having the most showed increases in CD8⁺ (P = .0017) and CD20⁺CD21^- counts (P = .0255), and a lower CD20⁺CD21⁺/CD20⁺ ratio (P = .0106) in the latter. Controls and persons with clotting disorders differ in CD4⁺ count. Among those with clotting factor disorders, there is no difference attributable to type of clotting disorder or factor therapy. Large amounts of treatment increased CD8⁺ and CD20⁺CD21^- counts, but were not associated with a change in CD4⁺ count.