Susceptibility to opportunistic infections in HIV-infected patients with increased CD4 T-cell counts on antiretroviral therapy may be predicted by markers of dysfunctional effector memory CD4 T cells and B cells
French, M.A., Keane, N.M., McKinnon, E.J., Phung, S. and Price, P. (2007) Susceptibility to opportunistic infections in HIV-infected patients with increased CD4 T-cell counts on antiretroviral therapy may be predicted by markers of dysfunctional effector memory CD4 T cells and B cells. HIV Medicine, 8 (3). pp. 148-155.
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Objectives: HIV-infected patients responding to combination antiretroviral therapy (ART) after experiencing severe immunodeficiency may exhibit persistent immune defects and occasionally experience opportunistic infections (OIs) despite increased CD4 T-cell counts. The investigation of immune defects in such patients was examined in this study. Methods: CD4 effector memory T-cell (T em-cell) function [assessed by blood cytomegalovirus (CMV) interferon-γ (IFN-γ) enzyme-linked immunosorbent spot-forming cell assay (ELISPOT) counts] and B-cell dysregulation [assessed by serum immunoglobulin A (IgA) and IgE levels] were examined in 27 patients with increased CD4 T-cell counts after receiving ART for over 2 years. Two of these patients and one other had developed OIs on ART and are described in detail. Results: Serum levels of IgA and IgE were higher than reference intervals (P<0.001) and CMV IFN-γ ELISPOT counts were lower than those in non-HIV-infected controls (P<0.001) in the HIV-infected patients. Low CMV IFN-γ ELISPOT counts were associated with high IgA levels (r = -0.5, P = 0.01, Spearman's correlation test) and segregated with high IgE levels (P = 0.06, Fisher's test). CMV IFN-γ ELISPOT counts and serum IgA and IgE levels did not change significantly over a median time of 35 (range 8-60) months after the first measurement, whereas CD4 T-cell counts increased. All three patients who experienced OIs had repeatedly low CMV IFN-γ ELISPOT counts and increased serum levels of IgA and/or IgE. Conclusion: Low CD4 T em-cell function and B-cell dysregulation are immune defects that may persist independently of changes in the CD4 T-cell count in HIV-1-infected patients responding to ART and are associated with an increased risk of developing an OI.
|Publication Type:||Journal Article|
|Murdoch Affiliation:||School of Chemical and Mathematical Science|
|Copyright:||© 2007 British HIV Association.|
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