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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
Author(s) -
French MA,
Keane NM,
McKin EJ,
Phung S,
Price P
Publication year - 2007
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/j.1468-1293.2007.00445.x
Subject(s) - elispot , immunology , medicine , immunoglobulin e , t cell , immune system , antibody
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.