Stimulation of the primary anti-HIV antibody response by IFN-α 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-alpha 2b. 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-alpha 2b (Group B, n = 30). Emergence of anti- HIV antibodies was monitored during 32 weeks by Western blot (WB) analyses of serum samples. IFN-alpha 2b treatment stimulated the production of anti- HIV antibodies. On Week 32, 19 weeks after the last IFN-alpha 2b 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-alpha 2b treatment also increased circulating concentrations of the B cellactivating 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.