title: The immunologic effects of maraviroc intensification in treated HIV-infected individuals with incomplete CD4+ T-cell recovery: a randomized trial.
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 1β) 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.
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA. phunt@php.ucsf.edu
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Shulman
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Hayes
authors.forename: Viktor
authors.initials: V
authors.lastname: Dahl
authors.forename: Ma
authors.initials: M
authors.lastname: Somsouk
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Funderburg
authors.forename: Bridget
authors.initials: B
authors.lastname: McLaughlin
authors.forename: Alan L
authors.initials: AL
authors.lastname: Landay
authors.forename: Oluwatoyin
authors.initials: O
authors.lastname: Adeyemi
authors.forename: Lee E
authors.initials: LE
authors.lastname: Gilman
authors.forename: Brian
authors.initials: B
authors.lastname: Clagett
authors.forename: Benigno
authors.initials: B
authors.lastname: Rodriguez
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Schacker
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Shacklett
authors.forename: Sarah
authors.initials: S
authors.lastname: Palmer
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
mesh_terms: D000328:Adult; D065100:CCR5 Receptor Antagonists; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D003510:Cyclohexanes / Q000627:therapeutic use*; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000276:immunology / Q000821:virology; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D023581:HIV Fusion Inhibitors / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000187:drug effects; D008221:Lymphoid Tissue / Q000187:drug effects / Q000276:immunology / Q000821:virology; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D012007:Rectum / Q000276:immunology / Q000473:pathology / Q000601:surgery; D014230:Triazoles / Q000627:therapeutic use*; D019562:Viral Load / Q000187:drug effects*
chemical_list: D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D023581:HIV Fusion Inhibitors; D012367:RNA, Viral; D014230:Triazoles; D000077592:Maraviroc