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 immunoglobulin (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) x 10(6)/liter and median pVL was 5.0 (range 3.2-5.2) log10 copies/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 log10, 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.
Vermeulen
Joost N
JN
IATEC, c/o Academic Medical Center of the University of Amsterdam, Amsterdam, the Netherlands. j.n.vermeulen@amc.uva.nl
Prins
Jan M
JM
Bunnik
Evelien
E
Hack
C Erik
CE
Jurriaans
Suzanne
S
Miedema
Frank
F
Lange
Joep M A
JM
Schuitemaker
Hanneke
H
D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
D016756:Immunoglobulins, Intravenous; D019394:Ki-67 Antigen; D012367:RNA, Viral