title: Addition of maraviroc to antiretroviral therapy decreased interferon-γ mRNA in the CD4+ T cells of patients with suboptimal CD4+ T-cell recovery.
abstract: 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-γ (IFN-γ) production in CD4+ T cells in vitro and in vivo, and evaluated the relationship between the mRNA level of IFN-γ and the degree of CD4+ T-cell count recovery. In vitro analysis indicated that MVC significantly decreased mRNA levels of IFN-γ in HIV-Tat stimulated CD4+ T cells from healthy donor peripheral blood mononuclear cells. Of the 18 HIV-infected 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-γ 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-γ decreased in both groups at 24 weeks. In conclusion, MVC decreased the mRNA level of IFN-γ 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-γ mRNA level and the larger decreased rate of IFN-γ mRNA in CD4+ T cells were associated with a good response to MVC regarding CD4+ T-cell recovery.
authors.affiliation: Internal Medicine, Clinical Research Institute, National Hospital Organization, Kyushu Medical Center, Fukuoka 810-8563, Japan. Electronic address: rumi373@kyumed.jp.
authors.forename: Rumi
authors.initials: R
authors.lastname: Minami
authors.affiliation: Internal Medicine, Clinical Research Institute, National Hospital Organization, Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Takahama
authors.affiliation: Internal Medicine, Clinical Research Institute, National Hospital Organization, Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kaku
authors.affiliation: Internal Medicine, Clinical Research Institute, National Hospital Organization, Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D003510:Cyclohexanes / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism; D014230:Triazoles / Q000627:therapeutic use*; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D003510:Cyclohexanes; D012333:RNA, Messenger; D012367:RNA, Viral; D014230:Triazoles; D007371:Interferon-gamma; D000077592:Maraviroc
keywords: CCR5 antagonist; CD4+ T-cell count; HIV-1; Interferon-γ