The suppression of immune activation during enfuvirtide-based salvage therapy is associated with reduced CCR5 expression and decreased concentrations of circulating interleukin-12 and IP-10 during 48 weeks of longitudinal follow-up.

Autor:	Carsenti-Dellamonica, H., Saïdi, H., Ticchioni, M., Guillouet de Salvador, F., Dufayard Cottalorda, J., Garraffo, R., Dellamonica, P., Durant, J., Gougeon, M.-L.
Předmět:	ENFUVIRTIDE (Drug) APOPTOSIS BLOOD cell count CELL receptors CHEMOKINES CYTOKINES HIV infections INTERLEUKINS LONGITUDINAL method NONPARAMETRIC statistics HEALTH outcome assessment POLYMERASE chain reaction REGRESSION analysis RESEARCH funding STATISTICS T cells U-statistics DATA analysis VIRAL load HIGHLY active antiretroviral therapy TREATMENT effectiveness BLOOD THERAPEUTICS
Zdroj:	HIV Medicine; Feb2011, Vol. 12 Issue 2, p65-77, 13p, 1 Chart, 6 Graphs
Abstrakt:	Background It has been suggested that patients who initiate highly active antiretroviral therapy (HAART) late in their course of infection may have suboptimal CD4 T-cell gains, persistent alterations in T-cell subsets and residual inflammation. To address this issue, we carried out a comprehensive 48-week immunological study in HIV-infected patients who had experienced failures of prior therapies, had low CD4 cell counts, and were receiving enfuvirtide-based salvage therapy. Methods Immunological monitoring of peripheral lymphocytes from enfuvirtide-responder patients was performed over a 48-week period. A detailed assessment of immune cell subsets, their activation state [CD38 and human leucocyte antigen (HLA)-DR expression] and homeostasis [activationinduced cell death (AICD) and Ki67 expression], and the expression of co-receptors was performed by flow cytometry. Cytokine and chemokine signatures were assessed using multianalyte profiling technology. Results Enfuvirtide-based salvage therapy induced a progressive restoration of naïve and central memory CD4 T cells, associated with a decrease in their activation state, suppression of premature priming for AICD and increased expression of Ki67. In addition, a significant decrease in C-C chemokine receptor 5 (CCR5) expression was detected on CD4 T cells, which was strongly correlated with the suppression of immune activation. Changes in circulating proinflammatory molecules occurred; i.e. there were decreases in the concentrations of interleukin (IL)-12, macrophage inflammatory protein MIP-1α, MIP-1β, monokine induced by IFNγ (MIG) and interferon-γ-inducible protein-10 (IP-10). The decline in circulating IL-12 and IP-10 was correlated with both the reduction in the viral load and CD4 T-cell restoration. Conclusions This study shows that suppression of HIV-1 replication with enfuvirtide-based salvage therapy in patients with low CD4 cell counts may result in an immunological benefit, characterized by the restoration of CD4 T-cell subsets associated with decreased immune activation and suppression of inflammation. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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