Intravenous immunoglobulin (IVIG) treatment for modulation of immune activation in human immunodeficiency virus type 1 infected therapy-naive individuals

We evaluated the ability of intravenous immunoglobuline (IVIG) to diminish immune hyperactivation, which is considered a major cause of CD4⁺ T cell loss during chronic HIV-1 infection and whether this affected CD4 ⁺ T cell counts and plasma HIV-1 RNA (pVL). Therefore, we treated six chronically HIV-1-infected, antiretroviral-therapy-naive patients with IVIG (0.4 g/kg) at weeks 0 and 4, with a follow-up of 12 weeks after the second dosage during which pVL, T cell numbers, and T cell activation were measured. At baseline median CD4⁺ T cell counts were 300 (range 200-460) × 10⁶/liter and median pVL was 5.0 (range 3.2-5.2) log ₁₀copies/ml. IgG plasma levels peaked during the first days after administration. We observed a decrease in the percentage of activated (CD38 ⁺ HLA-DR⁺) CD4⁺ and CD8⁺ T cells [3.5% (range 1-7%) and 5% (1-10%), respectively (p = 0.027)], but no effect on the fraction of proliferating CD4⁺ or CD8⁺ T cells as measured by Ki67 expression. CD4⁺ T cell counts were significantly increased on day 4 (median +55 cells, range 0-150, p = 0.043). pVL was significantly increased on day 1 after IVIG infusion (median +0.13 log ₁₀, range 0.01-0.55, p = 0.028). All these parameters returned to baseline levels within 1 week after infusion. In conclusion, administration of IVIG caused a temporary decrease in T cell activation and an increase in CD4⁺ T cell counts, despite an increase in pVL. Our results support the hypothesis that T cell activation, rather than direct HIV-1 infection, mediates the loss of CD4⁺ T cells and suggest that immunomodulating therapy in HIV-1 infection could indeed be effective.