title: Effect of the CCR5 antagonist maraviroc on the occurrence of immune reconstitution inflammatory syndrome in HIV (CADIRIS): a double-blind, randomised, placebo-controlled trial.
abstract: BACKGROUND
  Immune reconstitution inflammatory syndrome (IRIS) is a common complication of antiretroviral therapy (ART) in patients with HIV. IRIS is associated with an increased risk of admission to hospital and death. We assessed whether CCR5 blockade with maraviroc reduces the risk of IRIS.
  
  
  METHODS
  The CADIRIS study was a double-blind, randomised, placebo-controlled trial that recruited participants from five clinical sites in Mexico and one in South Africa and followed them for 1 year. Patients were eligible if they were adults with HIV, who were naive to ART, had CD4 count lower than 100 cells per μL and HIV RNA greater than 1000 copies per mL. Participants were randomly assigned (1:1) by permuted block randomisation to receive either maraviroc (600 mg twice daily) or placebo in addition to an ART regimen that included tenofovir, emtricitabine, and efavirenz for 48 weeks. Patients, care providers, and members of the research team were masked to treatment allocation. Clinical and laboratory evaluations were done at baseline, and weeks 2, 4, 8, 12, 16, 24, 48, and 60. The primary outcome was time to an IRIS event by 24 weeks. All patients who were randomly assigned contributed to the primary time-to-event analysis from the date of ART initiation until week 24, the time of an IRIS event or death. This trial is registered with ClinicalTrials.gov, number NCT00988780.
  
  
  RESULTS
  Between Dec 10, 2009, and Jan 17, 2012, we screened 362 patients; of whom 279 met the inclusion criteria and three refused to participate; thus 276 participants were randomly assigned (140 to receive maraviroc and 136 to receive placebo). 64 (23%) patients had IRIS events, 33 (24%) in the maraviroc group and 31 (23%) in the placebo group (p=0·74). No difference in the time to IRIS events was noted between the treatment groups (HR 1·08, 95% CI 0·66-1·77; log-rank test p=0·74). 37 participants (26%) in the maraviroc group had grade 3 or 4 adverse events compared with 24 (18%) in placebo group; p=0·072); 25 (18%) in the maraviroc group and 21 (15%) in the placebo group had serious treatment emergent adverse events (p=0·63).
  
  
  CONCLUSIONS
  Maraviroc had no significant effect on development of IRIS after ART initiation. Inclusion of this CCR5 inhibitor in an initial treatment regimen does not confer a meaningful protection from the occurrence of IRIS in people with advanced HIV infection.
  
  
  BACKGROUND
  Pfizer.
authors.affiliation: Departmento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", México DF, México.
authors.forename: Juan G
authors.initials: JG
authors.lastname: Sierra-Madero
authors.affiliation: Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Ellenberg
authors.affiliation: Clinical HIV Research Unit, Department of Internal Medicine, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Rassool
authors.affiliation: Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Tierney
authors.affiliation: Departmento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", México DF, México. Electronic address: p_belaunzaran@yahoo.co.uk.
authors.forename: Pablo F
authors.initials: PF
authors.lastname: Belaunzarán-Zamudio
authors.affiliation: Departmento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", México DF, México.
authors.forename: Alondra
authors.initials: A
authors.lastname: López-Martínez
authors.affiliation: Departmento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", México DF, México.
authors.forename: Alicia
authors.initials: A
authors.lastname: Piñeirúa-Menéndez
authors.affiliation: HIV-1 Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, PA, USA.
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Montaner
authors.affiliation: HIV-1 Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, PA, USA.
authors.forename: Livio
authors.initials: L
authors.lastname: Azzoni
authors.affiliation: Servicio de Infectología, Hospital General de México, México DF, México.
authors.forename: César Rivera
authors.initials: CR
authors.lastname: Benítez
authors.affiliation: HIV Pathogenesis Unit, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, MD, USA.
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
authors.affiliation: Unidad de VIH, Hospital Civil de Guadalajara, Guadalajara, Jalisco, México.
authors.forename: Jaime
authors.initials: J
authors.lastname: Andrade-Villanueva
authors.affiliation: Centro Ambulatorio para la Prevención y Atención del SIDA e Infecciones de Transmisión Sexual, León, Guanajuato, México.
authors.forename: Juan L
authors.initials: JL
authors.lastname: Mosqueda-Gómez
authors.affiliation: Center for AIDS Research, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Benigno
authors.initials: B
authors.lastname: Rodriguez
authors.affiliation: Clinical HIV Research Unit, Department of Internal Medicine, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.
authors.forename: Ian
authors.initials: I
authors.lastname: Sanne
authors.affiliation: Center for AIDS Research, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman