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4th International AIDS Society Conference on HIV Pathogenesis and TreatmentSydney, Australia - July 22 - 25, 2007 |
GBV-C INFECTION IS ASSOCIATED WITH LESS T CELL ACTIVATION IN RECENTLY HIV-1-INFECTED SUBJECTS AND IS INDEPENDENT OF HIV-1 VIRAL LOAD
IAS Conf HIV Pathog Treat 2007 Jul 22-25;4th: Abstract No. MOAA105
Maidana Giret M.T.1, Silva T.M.1, Levi J.E.2, Bassichetto K.C.3, Ana N.4, Sabino E.4, Palácios R.1, Kallás E.G.1
1Federal University of São Paulo, Medicine, São Paulo, Brazil, 2Institute of Tropical Diseases of São Paulo, São Paulo, Brazil, 3Public Health Department of São Paulo, São Paulo, Brazil, 4Blood Center of São Paulo, São Paulo, Brazil
OBJECTIVES: Many clinical studies suggested a beneficial effect of GBV-C in the HIV-1 pathogenesis. However, the mechanisms involved in such protection are not clear. Since recent evidence have demonstrated the importance of cellular activation in the pathogenesis of HIV-1 infection, we investigated the GBV-C effect on T cell activation in a cohort of recently HIV-1-infected subjects.
METHODS: Fourty recently HIV-1-infected subjects (24 GBV-C infected), identified by STARHS, were studied at enrollment into the cohort. T cell counts, expanded immunophenotyping by flow cytometry, GBV-C RNA detection by real-time PCR, and HIV-1 viral load were performed. Non-parametric univariated and multivariated analyses were carried out to identify variables associated with cellular activation, in models including GBV-C status, HIV-1 viral load, T lymphocyte counts, and expression of CD38 and CCR5.
RESULTS: We first confirmed the positive correlation between HIV-1 viral load and %CD38+CD8+ T cells (r=0.35, p<0.05), but also detected a high correlation between %CD38+CD8+ T cells and %CCR5+ CD8+ T cells (r=0.65, p<0.01), two markers of cellular activation. GBV-C infected sujects had lower %CD38+CD4+ T cells (32.9 vs. 43.5, p<0.05), %CD38+CD8+ T cells (39.7 vs. 65.5, p<0.05), %CCR5+CD4+ T cells (19.1 vs. 24.5, p<0.05), and %CCR5+CD8+ T cells (41.5 vs. 59.4, p<0.05). In regression models, GBV-C RNA+ status was associated with cellular activation markers, measured by %CCR5 in CD4+ or CD8+ T cells or %CD38+ in CD8+ T cells (all with p<0.05), independent to the HIV-1 viral load, CD4+ and CD8+ T cell counts.
CONCLUSIONS: In a controlled fashion, we clearly demonstrated the association between GBV-C viremia and lower T cell activation. This effect may be one of the key mechanisms involved in the protection conferred by this virus against progression to immunodeficiency.
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2007-07-22
MOAA105
Immune Activation in HIV Pathogenesis
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