Stimulation of the primary anti-HIV antibody response by IFN-alpha in patients with acute HIV-1 infection.
Type I IFNs are needed for the production of antiviral antibodies in mice; whether they also stimulate primary antibody responses in vivo during human viral infections is unknown. This was assessed in patients acutely infected with HIV-1 and treated with IFN-alpha2b. Patients with acute HIV-1 infection were randomized to receive antiretroviral therapy alone (Group A, n=60) or combined for 14 weeks with pegylated-IFN-alpha2b (Group B, n=30). Emergence of anti-HIV antibodies was monitored during 32 weeks by Western blot (WB) analyses of serum samples. IFN-alpha2b treatment stimulated the production of anti-HIV antibodies. On Week 32, 19 weeks after the last IFN-alpha2b administration, there were 8.5 (6.5-10.0) HIV WB bands (median, interquartile range) in Group B and 7.0 (5.0-10.0) bands in Group A (P=0.054), and band intensities were stronger in Group B (P<0.05 for p18, p24, p34, p40, and p55 HIV antigens). IFN-alpha2b treatment also increased circulating concentrations of the B cell-activating factor of the TNF family (P<0.001) and ex vivo production of IL-12 (P<0.05), reflecting its effect on innate immune cells. Withdrawal of antiretroviral treatment on Week 36 resulted in a lower rebound of HIV replication in Group B than in Group A (P<0.05). Therefore, type I IFNs stimulate the emerging anti-HIV immune response in patients with acute HIV-1 infection, resulting in an improved control of HIV replication. Type I IFNs are thus critical in the development of efficient antiviral immune responses in humans, including the production of antiviral antibodies.
Adalid-Peralta
Laura
L
INSERM U764, Clamart, France.
Godot
Véronique
V
Colin
Céline
C
Krzysiek
Roman
R
Tran
Thi
T
Poignard
Pascal
P
Venet
Alain
A
Hosmalin
Anne
A
Lebon
Pierre
P
Rouzioux
Christine
C
Chene
Genevieve
G
Emilie
Dominique
D
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000208:Acute Disease; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000917:Antibody Formation / Q000187:drug effects; D023241:Antiretroviral Therapy, Highly Active; D005602:France; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D019562:Viral Load
D019380:Anti-HIV Agents; D015483:HIV Antibodies; D007074:Immunoglobulin G; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b