Stimulation of the primary anti-HIV antibody response by IFN-alpha in patients with acute HIV-1 infection

Abstract

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.

Fig. 1

Progression of antibodies against HIV antigens. Presence of antibodies against HIV antigens was evaluated by WB analysis. (A) Results from typical patients (n=3 for Groups A and B) at enrollment and on Week 32. The positive control is from a chronically HIV-infected patient and the negative control from a HIV-uninfected individual. (B) Kinetics of antibodies against p55, p40, and p34. *, Group A, n = 30; ○, Group B, n = 15. Results are expressed as log₁₀ [antibody concentration (AU)+1;mean±SEM].

Fig. 2

High-avidity antibodies for HIV antigens and IFN-α2b treatment. The fraction (median, IQR) of high-avidity antibodies among IgG antibodies against p24, p55, and gp160 antigens was determined. Numbers for Groups A and B correspond to patients considered for the analysis (low avidity at enrollment and detectable antibodies thereafter). *, Group A; ○, Group B; P > 0.1 for all comparisons between Groups A and B.

Fig. 3

Anti-HIV mBL and IFN-α2b treatment. Numbers (median, IQR) of circulating, IgG-producing mBL (IgG-mBL; A) and HIV-specific mBL (HIV-mBL; B) were determined; (A and B) n = 30. The numbers of IgG- and HIV-mBL were 105 (97–152)/1 × 10³ B lymphocytes and <1/1 × 10⁶ B lymphocytes, respectively, in healthy individuals (n=9).

Fig. 4

IFN-α2b effect on rebound of HIV replication after HAART withdrawal. HAART was withdrawn on Week 36 and HIV viremia determined 14 days later. Horizontal bars represent medians.