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J Hassett, GF Gjerset, JW Mosley, MA Fletcher, E Donegan, JW Parker, RB Counts, LM Aledort, H Lee and MC Pike
Mount Sinai Medical Center, New York, NY.
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.
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