title: Maraviroc reduces the regulatory T-cell frequency in antiretroviral-naive HIV-infected subjects.
abstract: BACKGROUND
  Maraviroc is the first antiretroviral (ART) drug to target a human protein, the CCR5 coreceptor; however, the mechanisms of maraviroc-associated immunomodulation in human immunodeficiency virus (HIV)-infected subjects remain to be elucidated. Regulatory T cells (Tregs) play a key role in HIV-associated immunopathology and are susceptible to maraviroc-mediated CCR5 blockade. Our aim was to evaluate the effect of maraviroc on Tregs.
  
  
  METHODS
  We compared the effect of maraviroc-containing or -sparing combination ART (cART) on Tregs in ART-naive, HIV-infected subjects. Tregs were characterized as CD4(+)CD25(hi)FoxP3(+) on day 0, 8, and 30. Additional analysis on week 48 was performed in a subgroup of patients. The potential reduction in the frequency of Tregs among maraviroc-treated peripheral blood mononuclear cells (PBMCs) was also tested in vitro. The suppressive function of Tregs was also analyzed in maraviroc-treated Tregs.
  
  
  RESULTS
  We found that maraviroc significantly reduced the Treg frequency in both the short term and 1 year after treatment initiation. In vitro experiments showed a dose-dependent reduction in the Treg frequency after treatment of PBMCs with maraviroc, although their in vitro suppressive function was not altered.
  
  
  CONCLUSIONS
  These findings partially explain maraviroc-associated immunomodulatory effects and open new therapeutic expectations for the development of Treg-depleting immunotherapies.
authors.affiliation: Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville.
authors.forename: María Mar
authors.initials: MM
authors.lastname: Pozo-Balado
authors.affiliation: Laboratory of Molecular Immunobiology, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Martínez-Bonet
authors.affiliation: Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville.
authors.forename: Isaac
authors.initials: I
authors.lastname: Rosado
authors.affiliation: Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Ruiz-Mateos
authors.affiliation: Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville Department of Medical Microbiology and Immunology, University of California, Davis.
authors.forename: Gema
authors.initials: G
authors.lastname: Méndez-Lagares
authors.affiliation: Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville.
authors.forename: María Mar
authors.initials: MM
authors.lastname: Rodríguez-Méndez
authors.affiliation: Infectious Diseases and HIV/AIDS Unit, Department of Internal Medicine, Hospital Universitari de Tarragona Joan XXIII, Universitat Rovira i Virgili, IISPV, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Vidal
authors.affiliation: Laboratory of Molecular Immunobiology, Hospital General Universitario Gregorio Marañon, Madrid, Spain.
authors.forename: María Angeles
authors.initials: MA
authors.lastname: Muñoz-Fernández
authors.affiliation: Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville.
authors.forename: Yolanda María
authors.initials: YM
authors.lastname: Pacheco
authors.affiliation: Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville.
authors.forename: Manuel
authors.initials: M
authors.lastname: Leal
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D003510:Cyclohexanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000187:drug effects; D012189:Retrospective Studies; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*; D014230:Triazoles / Q000494:pharmacology*
chemical_list: C584933:CCR5 protein, human; D003510:Cyclohexanes; D023581:HIV Fusion Inhibitors; D019713:Receptors, CCR5; D014230:Triazoles; D000077592:Maraviroc
keywords: ART naives; HIV; maraviroc; regulatory T cells (Tregs)