Increased Soluble Fas in HIV-Infected Hemophilia Patients with CD4 + and CD8 + Cell Count Increases and Viral Load and Immune Complex Decreases

Abstract

Previous studies interpreted increases of soluble Fas (sFas) in the plasma during disease progression in HIV-infected patients as evidence of increased apoptosis of CD4⁺ lymphocytes. We studied whether sFas and sFas ligand (sFasL) plasma levels are associated with CD4⁺ and CD8⁺ lymphocyte counts, plasma viral load, and IgM, IgG, C3d, and gp120 complexes on circulating CD4⁺ blood lymphocytes in long-term surviving HIV-infected hemophilia patients, most of whom were receiving HAART. Twenty-six hemophilia patients who were infected with HIV in the early 1980s were investigated in 1997, 1998, and 1999. HAART was initiated in 1996 and 1997 in most patients. Lymphocyte subpopulations and immune complex-coated CD4⁺ lymphocytes in the blood were investigated by flow cytometry, plasma viral load (HIV-1 mRNA copies/ml plasma) was tested with HIV-1 QT Nuclisens kits, sFas (ng/ml) and sFasL (ng/ml) plasma levels were measured with MBL ELISA kits, and the in vitro response of patient lymphocytes was tested in cell cultures. During the period from 1997 to 1999 we observed an increase in sFas plasma levels (p = 0.003) as well as in CD4⁺ (p = 0.004) and CD8⁺ (p = 0.023) cell counts; a decrease in IgG (p = 0.047), C3d (p = 0.024), and gp120 (p = 0.001)-coated CD4⁺ lymphocytes in the blood; and a decrease in the number of impaired mitogen stimulation assays (p = 0.013). sFas was negatively associated with viral burden (r = -0.662, p = 0.0002) as well as with CD4⁺IgM⁺(r = -0.554, p = 0.004), CD4⁺IgG⁺ (r = -0.431, p = 0.031), CD4⁺C3d⁺ (r = -0.551, p = 0.041), and CD4⁺gp120⁺(r = -0.430, p = 0.041) blood lymphocytes, CD8⁺DR⁺ cell counts (r = -0.700, p = 0.016), and impaired in vitro responses of patient lymphocytes to PHA (r = -0.475, p = 0.016). sFasL was negatively associated with total lymphocyte counts (r = -0.433, p = 0.027), as well as with absolute numbers of CD3⁺ (r= -0.492, p = 0.011) and CD8⁺ (r = -0.432, p = 0.027) cells. We conclude that, contrary to expectations, sFas plasma levels increased in long-term surviving HIV-infected hemophilia patients receiving HAART, concomitant with increases in CD4⁺ and CD8⁺ cell counts. Increased sFas may reflect the growing pool of T lymphocytes that recovers because of a decreasing viral burden and a decreasing immune complex load of CD4⁺ lymphocytes.