title: Expansion of antibody secreting cells and modulation of neutralizing antibody activity in HIV infected individuals undergoing structured treatment interruptions.
abstract: BACKGROUND
  HIV-1 infection generates numerous abnormalities in the B cell compartment which can be partly reversed by antiretroviral therapy. Our aim was to evaluate the effects that re-exposure to HIV antigens might have on the frequency and functionality of antibody secreting cells (ASC) in patients undergoing structured treatment interruptions (STI). As re-exposure to viral antigens may also boost the production of (neutralizing) antibodies, we also assessed the neutralizing activities during STI cycles.
  
  
  METHODS
  Retrospective study of 10 patients undergoing 3 cycles of STI with 2 weeks on and 4 weeks off HAART. ASC frequencies were determined by flow cytometry in samples obtained at the beginning and the end of STI. Neutralization capacity, total IgG concentration and anti-gp120-IgG titres were evaluated.
  
  
  RESULTS
  As expected, median viral loads were higher at the end of STI compared to on-HAART time points. The level of CD27 and CD38 expressing ACS followed the same pattern; with ASC being elevated up to 16 fold in some patients (median increase of 3.5% ± 4.13). Eight out of 10 patients maintained stable total IgG levels during the study. After purifying IgG fractions from plasma, HIV-neutralizing activity was observed in the two subjects with highest anti-gp120 titers. In one of these patients the neutralizing activity remained constant while the other showed elevated neutralizing Ab after first STI and once treatment was reinitiated after the 2nd STI.
  
  
  CONCLUSIONS
  Our data suggest that STI and its associated transient increases in viral load drive the frequencies of ASC in an antigen-specific manner. In some subjects, this re-exposure to autologous virus boosts the presence of neutralizing antibodies, similar to what is seen after influenza vaccination. STI may not boost clinically beneficial nAb levels but offers opportunities to isolate nAb producing cells at considerably higher levels than in subjects with completely suppressed viral replication.
authors: Irsicaixa AIDS Research Institute - HIVACAT, Hospital Universitari Germans Trias y Pujol, Badalona, Spain.
authors: Anuska
authors: A
authors: Llano
authors: Jorge
authors: J
authors: Carrillo
authors: Beatriz
authors: B
authors: Mothe
authors: Lidia
authors: L
authors: Ruiz
authors: Silvia
authors: S
authors: Marfil
authors: Elisabet
authors: E
authors: García
authors: Eloísa
authors: E
authors: Yuste
authors: Víctor
authors: V
authors: Sánchez
authors: Bonaventura
authors: B
authors: Clotet
authors: Julià
authors: J
authors: Blanco
authors: Christian
authors: C
authors: Brander
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000276:immunology*; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; D057134:Antibodies, Neutralizing; D007074:Immunoglobulin G