title: Virologic and immunologic effects of adding maraviroc to suppressive antiretroviral therapy in individuals with suboptimal CD4+ T-cell recovery.
abstract: BACKGROUND
  Combination antiretroviral therapy (ART) suppresses HIV-1 replication, but does not restore CD4 T-cell counts in all individuals. To investigate the effects of maraviroc on HIV-1 persistence and the relations between virologic and immunologic parameters in individuals with incomplete CD4 T-cell recovery, we performed a prospective, open-label pilot trial in which maraviroc was added to a suppressive ART regimen for 24 weeks.
  
  
  METHODS
  A5256 was a single-arm trial in which individuals on suppressive ART with incomplete CD4 T-cell recovery added maraviroc for 24 weeks.
  
  
  METHODS
  We quantified low-level, residual viremia in plasma and total HIV-1 DNA and 2-long terminal repeat (2-LTR) circles in peripheral blood mononuclear cells before and after maraviroc intensification. We also evaluated markers of CD4 and CD8 T-cell immune activation (%CD38HLA-DR) and apoptosis (%caspase3/Bcl-2).
  
  
  RESULTS
  No effect of maraviroc was found on the probability of detectable plasma viremia (≥1 copy/ml; n = 31, exact McNemar P = 1.0) or detectable 2-LTR circles (n = 28, P = 0.25) or on total HIV-1 DNA (n = 28, 90% confidence interval -0.1, +0.3 log10 copies/10 CD4 T-cells). Premaraviroc HIV-1 DNA levels were inversely related to premaraviroc %CD38HLA-DR CD4 T-cells (Spearman = -0.52, P = 0.004), and lower premaraviroc HIV-1 DNA levels were associated with larger decreases in %CD38HLA-DR CD4 T-cells during maraviroc intensification (Spearman = 0.44, P = 0.018).
  
  
  CONCLUSIONS
  In individuals on suppressive ART with incomplete CD4 T-cell recovery, maraviroc intensification did not affect measures of HIV-1 persistence but did decrease persistent CD4 T-cell immune activation especially in individuals with low preintensification levels of HIV-1 DNA.
authors.affiliation: aDivision of Infectious Diseases, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania bCenter for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts cDivison of Infectious Diseases, Department of Medicine, Henry Ford Hospital, Detroit, Michigan dDepartment of Laboratory Medicine and Medicine, School of Medicine, University of Washington, Seattle, Washington eDepartment of Medicine, Rush University Medical Center, Chicago, Illinois fHIV Research Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland gDivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts hDavid Geffen School of Medicine, University of California Los Angeles, Los Angeles, California iDivision of Infectious Diseases, Weill Medical College, Cornell University, New York, New York, USA.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Cillo
authors.forename: Benedict B
authors.initials: BB
authors.lastname: Hilldorfer
authors.forename: Christina M
authors.initials: CM
authors.lastname: Lalama
authors.forename: John E
authors.initials: JE
authors.lastname: McKinnon
authors.forename: Robert W
authors.initials: RW
authors.lastname: Coombs
authors.forename: Allan R
authors.initials: AR
authors.lastname: Tenorio
authors.forename: Lawrence
authors.initials: L
authors.lastname: Fox
authors.forename: Rajesh T
authors.initials: RT
authors.lastname: Gandhi
authors.forename: Heather
authors.initials: H
authors.lastname: Ribaudo
authors.forename: Judith S
authors.initials: JS
authors.lastname: Currier
authors.forename: Roy M
authors.initials: RM
authors.lastname: Gulick
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Wilkin
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003510:Cyclohexanes / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D003510:Cyclohexanes; D014230:Triazoles; D000077592:Maraviroc