You are here
Maraviroc intensification in HIV-infected patients induces increased CCR5 expression on T cells
Assia Samri, Gael Mouillot, Christina Psomas, Melanie Lavenu, Selma Trabelsi, Lise Cuzin, Pierre Corbeau, Brigitte Autran, Philippe Flandre *Immunology, UPMC Univ Paris 06, UMR-S945, Laboratory Immunity and Infection, Inserm, U945, Laboratory Immunity and Infection, Paris, F-75013, France, Immunology, Infectious Diseases Department, University Hospital, Institute for Human Genetics, CNRS UPR1142, Montpellier, France, Immunology, INSERM U 943 and University Pierre and Marie Curie, UMRS 943, Paris, France, Immunology, Infectious Diseases Department, University Hospital, Toulouse, France, Immunology, Immunology Department, University Hospital, Nimes, Institute for Human Genetics, CNRS UPR1142, Montpellier, France
Background: Our group showed that Maraviroc (MVC) intensification over 24 weeks (W) in immunological non responders over the last two years (CD4<350 cells/mm3, CD4 slope <50 cells/mm3/year and HIV-RNA<50 copies/ml) enhanced CD4 cell slopes and significantly decreased CD8+ T cell activation#. We analyzed whether these effects were associated with modulation of CCR5 expression on various T cell subsets, frequencies of virusspecific T cells and levels of CCR5 ligands.
Methodology: 31 patients were monitored at baseline, after 24W of MVC intensification and at W28 (4W post-intensification). We evaluated CCR5 modulation on different T-cell subsets (Naive (N), Central-Memory (CM), Effector-Memory (EM), Effector (E) and on CD4 T cells expressing CXCR3, CCR4 or CCR6, as well as on activated CD4+ and CD8+ T cells in parallel to plasma CCR5 ligands (MIP-1A, MIP-1B and RANTES) levels. T cells specific for HIV-1 gag and CMV antigens were quantified using IFN-G ELISpot assay.
Results: During MVC intensification, a decrease in activated CD8+DR+CD38+ T cells is observed (-26%; p=0.001). We also observe to a significant increase of CCR5 on CD4+ (+6%; <0.001) and CD8+ T cells (+15%; p<0.001), mainly on CD8+ TEM (+14%; p=0.003) and on activated CD8+DR+38+ T cells (+10%; p=0.00014). MVC intensification also resulted in significant increase in CCR5 expression on CD4+CXCR3-CCR4+CCR6+ T cells defining Th17 cells (+4%; p=0.003). This increased CCR5 expression paralleled an increase in MIP-1B plasma levels (+57pg/ml; p=<0.001). At W28, 4 weeks after stopping MVC both CCR5 expression and MIP-1B levels were reversed. No significant changes were observed in frequencies of CMVor HIV-specific T cells.
Conclusions: The blockade of CCR5 receptor-ligand interaction by MVC not only reduced CD8+ T-cell activation but also increased CCR5 expression mainly on effector-memory and activated T cells, paralleling the increase in plasma levels of MIP-1B the CCR5 ligand. These changes during MVC intensification might reflect a preferential decrease of activated T cells that do not display CCR5 and the redistribution of CCR5+ activated differentiated T cells in association with the positive effect on CD4 counts in immunological non responders. # Cuzin L. et al. Maraviroc Intensification of Stable Antiviral Therapy in HIV-1-Infected Patients With Poor Immune Restoration: MARIMUNO-ANRS 145 Study. J Acquir Immune Defic Syndr. 2013 Apr 1;62(4).