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

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-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.

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.

• Authors: Ma French, Nm Keane, Ej McKinnon, S Phung, P Price
• Journal: HIV medicine (HIV Med) Vol. 8 Issue 3 Pg. 148-55 (Apr 2007) ISSN: 1464-2662 [Print] England
• PMID: 17461858 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• Immunoglobulins
• Interferon-gamma

Topics

• AIDS-Related Opportunistic Infections (immunology, microbiology)
• Adult
• Aged
• Anti-HIV Agents (therapeutic use)
• Aspergillosis (drug therapy, immunology, virology)
• Aspergillus fumigatus (growth & development)
• CD4 Lymphocyte Count
• Enzyme-Linked Immunosorbent Assay
• HIV (immunology)
• HIV Infections (drug therapy, immunology, microbiology, virology)
• Humans
• Immunoglobulins (blood)
• Immunologic Memory (immunology)
• Interferon-gamma (blood)
• Middle Aged
• Mycobacterium avium Complex (growth & development)
• Mycobacterium avium-intracellulare Infection (drug therapy, immunology, virology)