Chronic HIV-1 infection induces B-cell dysfunction that is incompletely resolved by long-term antiretroviral therapy

© 2015 Wolters Kluwer Health, Inc. All rights reserved. Objectives: To determine the effect of long-term antiretroviral therapy (ART) on HIV-1-induced B-cell dysfunction. Design: Comparative study of ART-naive and ART-treated HIVinfected patients with non-HIV controls. Methods: B-cell dysfunction was examined in patients with HIV-1 infection (n = 30) who had received ART for a median time of 9.25 years (range: 1.3-21.7) by assessing proportions of CD21lo/-B cells (a marker of B-cell exhaustion) and proportions of tumor necrosis factor-related apoptosis-inducing ligand+ or B and T lymphocyte attenuator+ B cells, and serum levels of immunoglobulin free light chains (markers of B-cell hyperactivation). The association of these markers with serum levels of IgG1 and IgG2, and production of IgG antibodies after vaccination with pneumococcal polysaccharides were also examined. ART-naive patients with HIV (n = 20) and controls (n = 20) were also assessed for comparison. Results: ART-treated patients had increased proportions of CD21lo/-and tumor necrosis factor-related apoptosis-inducing ligand+ B cells and, furthermore, although proportions of B and T lymphocyte attenuator+ B cells were not significantly different from controls, they correlated negatively with CD21lo/-B cells. Proportions of CD21lo/-B cells also correlated negatively with current CD4+ T-cell counts. In ART-naive patients with HIV, free light chains correlated with CD21lo/-B cells and IgG1, but not IgG2. Serum IgG2:IgG1 ratios were substantially lower than normal in patients with HIV and did not resolve on ART. In ART-treated patients, IgG antibody responses to pneumococcal polysaccharides after vaccination were not associated with markers of B-cell dysfunction. Conclusions: B-cell dysfunction persists in patients with HIV receiving long-term ART. The causes and consequences of this require further investigation.