title: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of a Chemokine Receptor 5 (CCR5) Antagonist to Decrease the Occurrence of Immune Reconstitution Inflammatory Syndrome in HIV-Infection: The CADIRIS Study.
abstract: BACKGROUND
  Immune Reconstitution Inflammatory Syndrome (IRIS) is a common complication of antiretroviral therapy (ART) in HIV-infected patients. IRIS is associated with an increased risk of hospitalization and death. We ascertained whether CCR5 blockade using maraviroc reduces the risk of IRIS.
  
  
  METHODS
  The CADIRIS study was a randomized, double-blind, placebo-controlled, clinical trial that accrued subjects from five clinical sites in Mexico and one in South Africa between November 2009 and January 2012, and followed them for one year. The primary outcome was occurrence of IRIS by 24 weeks. HIV-infected adults, naïve to ART, with CD4 cells <100/μL, and HIVRNA >1,000 copies/mL were eligible. We screened 362 subjects; 279 met inclusion criteria, 3 refused participation, and 276 were randomized. Participants received maraviroc 600 mg twice daily or placebo added to an ART regimen that included tenofovir, emtricitabine, and efavirenz for 48 weeks.
  
  
  RESULTS
  There were 276 patients randomized (140 received maraviroc and 136 placebo). There was no difference in the time to IRIS events between treatment arms (HR 1·08, 95% CI (0·66, 1·77), log-rank testp=0·743). In total, 64 (23%) patients had IRIS events, 33 (24%) in the maraviroc arm and 31 (23%) in the placebo arm (p=0·88).
  
  
  CONCLUSIONS
  Maraviroc had no significant effect on frequency, time or severity of IRIS events after ART initiation. Including a CCR5 inhibitor in an initial treatment regimen does not confer a meaningful protection from the occurrence of IRIS in persons with advanced HIV infection.
  
  
  BACKGROUND
  The trial was funded as investigator initiated research by Pfizer Inc, New York, NY, USA.
  
  
  BACKGROUND
  ClinicalTrials.gov. ID: NCT00988780 (http://clinicaltrials.gov/ct2/show/NCT00988780).
authors.affiliation: Departmento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán". Vasco de Quiroga 15, Col. Sección XVI, Del. Tlalpan. México DF, México. CP 14000.
authors.forename: Juan G
authors.initials: JG
authors.lastname: Sierra-Madero
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine. 611 Blockley Hall. 423 Guardian Drive, Philadelphia, PA 19104-602. USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Ellenberg
authors.affiliation: Clinical HIV Research Unit, Department of Internal Medicine, Faculty of Health Sciences, University of Witwatersrand. Perth Ave, Westdene. Johannesburg, South Africa.
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Rassool
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine. 611 Blockley Hall. 423 Guardian Drive, Philadelphia, PA 19104-602. USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Tierney
authors.affiliation: Departmento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán". Vasco de Quiroga 15, Col. Sección XVI, Del. Tlalpan. México DF, México. CP 14000.
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". Vasco de Quiroga 15, Col. Sección XVI, Del. Tlalpan. México DF, México. CP 14000.
authors.forename: Alondra
authors.initials: A
authors.lastname: López-Martínez
authors.affiliation: Departmento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán". Vasco de Quiroga 15, Col. Sección XVI, Del. Tlalpan. México DF, México. CP 14000.
authors.forename: Alicia
authors.initials: A
authors.lastname: Piñeirúa-Menéndez
authors.affiliation: HIV-1 Immunopathogenesis Laboratory, The Wistar Institute. 3601 Spruce Street, Philadelphia, PA 19104. USA.
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Montaner
authors.affiliation: HIV-1 Immunopathogenesis Laboratory, The Wistar Institute. 3601 Spruce Street, Philadelphia, PA 19104. USA.
authors.forename: Livio
authors.initials: L
authors.lastname: Azzoni
authors.affiliation: Servicio de Infectología, Hospital General de México, Dr. Balmis 148, Col. Doctores. México DF, México. CP 06726.
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. 10 Center Drive, Building 10, 11C-103. Bethesda, MD 20892.
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
authors.affiliation: Unidad de VIH, Hospital Civil de Guadalajara. Calle Hospital 278 S.H. Col. Alcalde Barranquitas. Guadalajara, Jalisco, México. CP 44280.
authors.forename: Jaime
authors.initials: J
authors.lastname: Andrade-Villanueva
authors.affiliation: Centro de Ambulatorio de Prevención y Atención en SIDA e Infecciones de Transmisión Sexual León. Calle 20 de enero # 927, Col. Obregón. León, Guanajuato, México CP 37000.
authors.forename: Juan L
authors.initials: JL
authors.lastname: Mosqueda-Gómez
authors.affiliation: Center for AIDS Research, Case Western Reserve University. 2061 Cornell Rd, Cleveland OH 44106. 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. Perth Ave, Westdene. Johannesburg, South Africa ; Center for International Development, Boston University. USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Sanne
authors.affiliation: Center for AIDS Research, Case Western Reserve University. 2061 Cornell Rd, Cleveland OH 44106. USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman