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

作者：Carsenti Dellamonica H; Saidi H; Ticchioni M; de Salvador F Guillouet; Cottalorda J Dufayard; Garraffo R; Dellamonica P; Durant J; Gougeon M L^*

来源：HIV Medicine, 2011, 12(2): 65-77.

DOI：10.1111/j.1468-1293.2010.00848.x

• apoptosis
• enfuvirtide-based salvage therapy
• HIV-1
• HIV co-receptors
• interferon-gamma-inducible protein-10 (IP-10)
• interleukin-12

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 [activation-induced 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 naive 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-1 alpha, MIP-1 beta, monokine induced by IFN gamma (MIG) and interferon-gamma-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.

• 出版日期2011-2