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- Title
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.
- Authors
Carsenti-Dellamonica, H.; Saïdi, H.; Ticchioni, M.; Guillouet de Salvador, F.; Dufayard Cottalorda, J.; Garraffo, R.; Dellamonica, P.; Durant, J.; Gougeon, M.-L.
- Abstract
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.
- Subjects
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
- Publication
HIV Medicine, 2011, Vol 12, Issue 2, p65
- ISSN
1464-2662
- Publication type
Article
- DOI
10.1111/j.1468-1293.2010.00848.x