Expansion of antibody secreting cells and modulation of neutralizing antibody activity in HIV infected individuals undergoing structured treatment interruptions.

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.

Conclusion: 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.