title: Maraviroc, as a Switch Option, in HIV-1-infected Individuals With Stable, Well-controlled HIV Replication and R5-tropic Virus on Their First Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Plus Ritonavir-boosted Protease Inhibitor Regimen: Week 48 Results of the Randomized, Multicenter MARCH Study.
abstract: Alternative combination antiretroviral therapies in virologically suppressed human immunodeficiency virus (HIV)-infected patients experiencing side effects and/or at ongoing risk of important comorbidities from current therapy are needed. Maraviroc (MVC), a chemokine receptor 5 antagonist, is a potential alternative component of therapy in those with R5-tropic virus.
  
  
  
  The Maraviroc Switch Study is a randomized, multicenter, 96-week, open-label switch study in HIV type 1-infected adults with R5-tropic virus, virologically suppressed on a ritonavir-boosted protease inhibitor (PI/r) plus double nucleoside/nucleotide reverse transcriptase inhibitor (2 N(t)RTI) backbone. Participants were randomized 1:2:2 to current combination antiretroviral therapy (control), or replacing the protease inhibitor (MVC + 2 N(t)RTI arm) or the nucleoside reverse transcriptase inhibitor backbone (MVC + PI/r arm) with twice-daily MVC. The primary endpoint was the difference (switch minus control) in proportion with plasma viral load (VL) <200 copies/mL at 48 weeks. The switch arms were judged noninferior if the lower limit of the 95% confidence interval (CI) for the difference in the primary endpoint was < -12% in the intention-to-treat (ITT) population.
  
  
  
  The ITT population comprised 395 participants (control, n = 82; MVC + 2 N(t)RTI, n = 156; MVC + PI/r, n = 157). Baseline characteristics were well matched. At week 48, noninferior rates of virological suppression were observed in those switching away from a PI/r (93.6% [95% CI, -9.0% to 2.2%] and 91.7% [95% CI, -9.6% to 3.8%] with VL <200 and <50 copies/mL, respectively) compared to the control arm (97.6% and 95.1% with VL <200 and <50 copies/mL, respectively). In contrast, MVC + PI/r did not meet noninferiority bounds and was significantly inferior (84.1% [95% CI, -19.8% to -5.8%] and 77.7% [95% CI, -24.9% to -8.4%] with VL <200 and <50 copies/mL, respectively) to the control arm in the ITT analysis.
  
  
  
  These data support MVC as a switch option for ritonavir-boosted PIs when partnered with a 2-N(t)RTI backbone, but not as part of N(t)RTI-sparing regimens comprising MVC with PI/r.
  
  
  
  NCT01384682.
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia Medical Research Council Clinical Trials Unit, Institute of Clinical Trials and Methodology Clinical Research Group, Infection and Population Health, University College London, United Kingdom.
authors.forename: Sarah Lilian
authors.initials: SL
authors.lastname: Pett
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia.
authors.forename: Janaki
authors.initials: J
authors.lastname: Amin
authors.affiliation: Wojewodzki Szpital Zakazny Centrum Diagnostyki i Terapii AIDS, Warsaw, Poland.
authors.forename: Andrejz
authors.initials: A
authors.lastname: Horban
authors.affiliation: Hospital Civil de Guadalajara "Fray Antonio Alcalde," Jalisco, Mexico.
authors.forename: Jaime
authors.initials: J
authors.lastname: Andrade-Villanueva
authors.affiliation: Hospital General de Agudos J M Ramos Mejia Fundación IBIS Coordinacion de Investigacion Clinica Academica en Latinoamerica.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Losso
authors.affiliation: Fundación Infectologia de Atencion Ambulatoria, Buenos Aires, Argentina.
authors.forename: Norma
authors.initials: N
authors.lastname: Porteiro
authors.affiliation: Instituto Nacional de Ciencias Medicas y Nutriciòn Salvador Zubiran, Tlalpan, Mexico.
authors.forename: Juan
authors.initials: J
authors.lastname: Sierra Madero
authors.affiliation: Fundación IBIS Coordinacion de Investigacion Clinica Academica en Latinoamerica Hospital Italiano de Buenos Aires, Argentina.
authors.forename: Waldo
authors.initials: W
authors.lastname: Belloso
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia.
authors.forename: Elise
authors.initials: E
authors.lastname: Tu
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Silk
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia St Vincent's Hospital, Sydney, Australia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Kelleher
authors.affiliation: British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Harrigan
authors.affiliation: ViiV Healthcare Ltd, London, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Clark
authors.affiliation: Nagoya Medical Centre, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Sugiura
authors.affiliation: Fundacion Arriaran, Santiago, Chile.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Wolff
authors.affiliation: Southern Alberta Clinic, Calgary, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Gill
authors.affiliation: Hospital Clinic de Barcelona, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Gatell
authors.affiliation: Brighton and Sussex University Hospitals National Health Service Trust, Brighton, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Fisher
authors.affiliation: Brighton and Sussex University Hospitals National Health Service Trust, Brighton, United Kingdom.
authors.forename: Amanda
authors.initials: A
authors.lastname: Clarke
authors.affiliation: HIV Netherlands, Australia, Thailand Research Collaboration, Bangkok.
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
authors.affiliation: Orleans Hospital (Centre Hospitalier Regional D'Orleans Orleans La Source), France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Prazuck
authors.affiliation: Institut für Virologie, Cologne, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Kaiser
authors.affiliation: Monash Medical Centre, Melbourne, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Woolley
authors.affiliation: Fundacion Clinic Spain Clinical Trials Unit, Barcelona.
authors.forename: Juan Alberto
authors.initials: JA
authors.lastname: Arnaiz
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia St Vincent's Hospital, Sydney, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Cooper
authors.affiliation: Department of Medicine I, University Hospital Bonn, Germany.
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Rockstroh
authors.affiliation: Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Mallon
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia.
authors.forename: Sean
authors.initials: S
authors.lastname: Emery
mesh_terms: D000328:Adult; D015897:Comorbidity; D003510:Cyclohexanes / Q000627:therapeutic use*; D005260:Female; D023581:HIV Fusion Inhibitors / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use*; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D019562:Viral Load; D014779:Virus Replication
chemical_list: D003510:Cyclohexanes; D023581:HIV Fusion Inhibitors; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D014230:Triazoles; D000077592:Maraviroc; D019438:Ritonavir
keywords: HIV-1; antiretroviral; comorbidity; maraviroc; switch