title: 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.
abstract: OBJECTIVE
  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-gamma (IFN-gamma) 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-gamma ELISPOT counts were lower than those in non-HIV-infected controls (P<0.001) in the HIV-infected patients. Low CMV IFN-gamma 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-gamma 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-gamma ELISPOT counts and increased serum levels of IgA and/or IgE.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Immunology, Royal Perth Hospital, and School of Surgery and Pathology, University of Western Australia, Perth, Western Australia, Australia. martyn.french@health.wa.gov.au
authors.forename: Ma
authors.initials: M
authors.lastname: French
authors.forename: Nm
authors.initials: N
authors.lastname: Keane
authors.forename: Ej
authors.initials: E
authors.lastname: McKinnon
authors.forename: S
authors.initials: S
authors.lastname: Phung
authors.forename: P
authors.initials: P
authors.lastname: Price
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000276:immunology* / Q000382:microbiology; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use; D001228:Aspergillosis / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D001232:Aspergillus fumigatus / Q000254:growth & development*; D018791:CD4 Lymphocyte Count; D004797:Enzyme-Linked Immunosorbent Assay; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007156:Immunologic Memory / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood; D008875:Middle Aged; D015269:Mycobacterium avium Complex / Q000254:growth & development*; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy / Q000276:immunology / Q000821:virology*
chemical_list: D019380:Anti-HIV Agents; D007136:Immunoglobulins; D007371:Interferon-gamma