The effect of combination antiretroviral therapy on CD5 B-cells, B-cell activation and hypergammaglobulinaemia in HIV-1-infected patients

Objectives This study assessed B-cell activation, CD5 B-cells and circulating immunoglobulin levels in HIV-infected patients treated with combination antiretroviral therapy (CART). Methods Measurement of plasma immunoglobulin levels and electrophoresis of plasma proteins, and analyses of total numbers of B-cells and B-cells expressing CD38 and CD5 in whole blood, were undertaken in 47 consecutive HIV-1-infected patients attending an out-patient clinic. Results All HIV-infected patients had similar percentages and numbers of B-cells. Proportions of CD5 B-cells in all HIV-infected patients were significantly lower than those in HIV-negative controls. Aviraemic HIV-infected patients on CART had lower percentages of CD5, CD38 and CD5 CD38 B-cell subsets and lower plasma levels of immunoglobulin G (IgG) and immunoglobulin A (IgA) than viraemic HIV-infected patients (untreated or on CART). However, 33-37% of aviraemic W-infected patients had IgG and IgA levels above the 95th percentile of the normal range defined in HIV-seronegative donors. In aviraemic HIV-infected patients, plasma IgA levels correlated only with proportions of activated (CD38) B-cells. IgG levels did not correlate with the proportions of B-cell subsets or any marker of HIV disease activity. Monoclonal immunoglobulins were not detected in any plasma sample. Conclusions Aviraemic HIV-infected patients on CART have lower plasma levels of IgG and IgA than viraemic HIV-infected patients, but levels are often above the normal range. CD5 B-cell numbers are depressed, so these cells are unlikely to contribute to hypergammaglobulinaemia in HIV-infected patients.