Abstract
BackgroundHIV-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.MethodsRetrospective 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.ResultsAs 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.ConclusionsOur 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.
Highlights
HIV-1 infection generates numerous abnormalities in the B cell compartment which can be partly reversed by antiretroviral therapy
Expansion of antibody secreting cells (ASC) frequencies after structured treatment interruptions (STI) are driven by HIV viral loads In order to examine the effect of STI on ASC populations and its correlation with changes in HIV viral load, the frequencies of ASC in the peripheral blood were determined for 10 individuals undergoing 3 cycles of STI
Five of the 10 patients: patients # 2, 3, 6, 7 and 8 (2 without IL2 [patients # 2 and 3] and 3 with IL2-treatment [patients # 6, 7 and 8], respectively) showed a rapid viral rebound after treatment interruption to at least 103 viral copies/ml, whereas the remaining five individuals always maintained their viral loads to
Summary
HIV-1 infection generates numerous abnormalities in the B cell compartment which can be partly reversed by antiretroviral therapy. Clinical parameters to assess HIV disease progression focus largely on CD4 T cell counts and CD4/CD8 T cell ratio, yet the B cell compartment of HIV infected subjects can be severely impacted by chronic HIV infection as well This includes hypergammaglobulinaemia [1,2] and many other alterations in different B cell subpopulations, such as increased frequencies of immature transitional B cells, expansion of activated mature B cells, increased levels of memory B cells with an exhausted phenotype and a pronounced loss of resting memory B cells [3,4,5,6,7,8]. These differences were maintained after one year on HAART of both early and chronically HIV-infected individuals and were associated with a better functional profile of memory B cells in early treated subjects
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