Addition of maraviroc to antiretroviral therapy decreased interferon-gamma mRNA in the CD4+T cells of patients with suboptimal CD4+T-cell recovery

摘要

The CCR5 antagonist, maraviroc (MVC), is associated with an enhanced CD4+ T-cell response independent of virological suppression; however, its mechanism of action has not been elucidated. In this study, we confirmed the effect of MVC on CD4+ T-cell count recovery in immunological non-responders, and compared the conventional combination antiretroviral therapy (cART) with MVC-intensified cART. We also investigated the effect of MVC on interferon-gamma (IFN-gamma) production in CD4+ T cells in vitro and in vivo, and evaluated the relationship between the mRNA level of IFN-gamma and the degree of CD4+ T-cell count recovery. In vitro analysis indicated that MVC significantly decreased mRNA levels of IFN-gamma in HIV-Tat stimulated CD4+ T cells from healthy donor peripheral blood mononuclear cells. Of the 18 HIVinfected patients treated with MVC-intensified cART, 12 had a significantly increased CD4+ T-cell count after 24 weeks of additional treatment with MVC. In patients exhibiting a response in CD4+ T-cell counts, mRNA levels of IFN-gamma in CD4+ T cells were lower than those in patients showing a non-response at baseline and at week 24, while mRNA levels of IFN-gamma decreased in both groups at 24 weeks. In conclusion, MVC decreased the mRNA level of IFN-gamma in CD4+ T cells in vitro and in vivo, especially in patients whose CD4+ T-cell count increased significantly. We also found that the lower baseline IFN-gamma mRNA level and the larger decreased rate of IFN-gamma mRNA in CD4+ T cells were associated with a good response to MVC regarding CD4+ T-cell recovery. (C) 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.