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 HIV-infected 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 CD21 lo/-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 CD21 lo/-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 CD21 lo/-B cells. Proportions of CD21 lo/-B cells also correlated negatively with current CD4+ T-cell counts. In ART-naive patients with HIV, free light chains correlated with CD21 lo/-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.