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Interferon-Gamma responses to candida recover slowly or remain low in immunodeficient HIV patients responding to ART

Burgess, K., Price, P., James, I.R., Stone, S.F., Keane, N.M., Lim, A.Y.F., Warmington, J.R. and French, M.A. (2006) Interferon-Gamma responses to candida recover slowly or remain low in immunodeficient HIV patients responding to ART. Journal of Clinical Immunology, 26 (2). pp. 160-167.

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Extended assessments of memory T-cell responses in HIV patients who have a satisfactory virological response to combination antiretroviral therapy (CART) have been limited by availability of longitudinal samples and of antigens to which most individuals (including HIV-negative controls) have been exposed. Studies of cytomegalovirus (CMV) show that interferon-gamma (IFN-;3) responses never recover completely, but this may be antigen-specific. Here we present responses to Candida and CMV antigens analyzed using a statistical approach that derives overall trends from samples collected at variable time points. Results were considered in relation to putative markers of T-regulatory cells. Blood mononuclear cells collected from seventeen HIV-1 patients (nadir <100 CD4 T cells/mL) 0 138 years after initiation of CART were stimulated with Candida spp lysate, Candida enolase protein or CMV lysate and production of IFN-;3 was assessed by ELISpot assay. CD4 T-cell counts increased fivefold and stabilized within 24 months on CART, following control of plasma viremia. IFN-;3 responses to Candida antigens began low and increased slowly, generating positive slope up to 60 months on CART (Candida enolase p=0.008; Candida lysate p=0.03; mixed-model Wald test). Only two patients displayed a CMV or Candida-specific IFN-;3 response above the median for seronegative controls. Proportions of T cells expressing CD25 or CD57 did not correlate with IFN-;3 responses. Slow reconstitution of IFN-;3 responses to CMV and Candida in previously immunodeficient patients with restored CD4+ T-cell counts on CART suggests a broad and nonresolving defect in memory T-cell responses.

Publication Type: Journal Article
Murdoch Affiliation: Centre for Clinical Immunology and Biomedical Statistics
Publisher: Springer US
Copyright: 2006 Springer Science + Business Media, Inc.
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