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Blood ; 121(23): 4635-46, 2013 Jun 06.
Article in English | MEDLINE | ID: mdl-23589670

ABSTRACT

The CCR5 inhibitor maraviroc has been hypothesized to decrease T-cell activation in HIV-infected individuals, but its independent immunologic effects have not been established in a placebo-controlled trial. We randomized 45 HIV-infected subjects with CD4 counts <350 cells per mm(3) and plasma HIV RNA levels <48 copies per mL on antiretroviral therapy (ART) to add maraviroc vs placebo to their regimen for 24 weeks followed by 12 weeks on ART alone. Compared with placebo-treated subjects, maraviroc-treated subjects unexpectedly experienced a greater median increase in % CD38+HLA-DR+ peripheral blood CD8+ T cells at week 24 (+2.2% vs -0.7%, P = .014), and less of a decline in activated CD4+ T cells (P < .001). The % CD38+HLA-DR+ CD4+ and CD8+ T cells increased nearly twofold in rectal tissue (both P < .001), and plasma CC chemokine receptor type 5 (CCR5) ligand (macrophage-inflammatory protein 1ß) levels increased 2.4-fold during maraviroc intensification (P < .001). During maraviroc intensification, plasma lipopolysaccharide declined, whereas sCD14 levels and neutrophils tended to increase in blood and rectal tissue. Although the mechanisms explaining these findings remain unclear, CCR5 ligand-mediated activation of T cells, macrophages, and neutrophils via alternative chemokine receptors should be explored. These results may have relevance for trials of maraviroc for HIV preexposure prophylaxis and graft-versus-host disease. This trial was registered at www.clinicaltrials.gov as #NCT00735072.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Cyclohexanes/therapeutic use , Graft vs Host Disease/immunology , HIV Infections/immunology , HIV-1/immunology , Triazoles/therapeutic use , Viral Load/drug effects , Adult , CCR5 Receptor Antagonists , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/virology , Female , Gastrointestinal Tract/drug effects , Gastrointestinal Tract/immunology , Gastrointestinal Tract/virology , Graft vs Host Disease/drug therapy , Graft vs Host Disease/virology , HIV Fusion Inhibitors/therapeutic use , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/drug effects , Humans , Immunophenotyping , Lymphocyte Activation/drug effects , Lymphoid Tissue/drug effects , Lymphoid Tissue/immunology , Lymphoid Tissue/virology , Male , Maraviroc , Middle Aged , RNA, Viral/blood , RNA, Viral/genetics , Rectum/immunology , Rectum/pathology , Rectum/surgery
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