PMID- 26366430 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20191120 IS - 2352-3018 (Electronic) IS - 2352-3018 (Linking) VI - 1 IP - 2 DP - 2014 Nov 1 TI - 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. PG - e60-e67 AB - 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, naive to ART, with CD4 cells <100/muL, 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. FINDINGS: 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 test p=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). INTERPRETATION: 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. FUNDING: The trial was funded as investigator initiated research by Pfizer Inc, New York, NY, USA. TRIAL REGISTRATION: ClinicalTrials.gov. ID: NCT00988780 (http://clinicaltrials.gov/ct2/show/NCT00988780). FAU - Sierra-Madero, Juan G AU - Sierra-Madero JG AD - Departmento de Infectologia, Instituto Nacional de Ciencias Medicas y Nutricion "Salvador Zubiran". Vasco de Quiroga 15, Col. Seccion XVI, Del. Tlalpan. Mexico DF, Mexico. CP 14000. FAU - Ellenberg, Susan AU - Ellenberg S AD - Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine. 611 Blockley Hall. 423 Guardian Drive, Philadelphia, PA 19104-602. USA. FAU - Rassool, Mohammed S AU - Rassool MS AD - Clinical HIV Research Unit, Department of Internal Medicine, Faculty of Health Sciences, University of Witwatersrand. Perth Ave, Westdene. Johannesburg, South Africa. FAU - Tierney, Ann AU - Tierney A AD - Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine. 611 Blockley Hall. 423 Guardian Drive, Philadelphia, PA 19104-602. USA. FAU - Belaunzaran-Zamudio, Pablo F AU - Belaunzaran-Zamudio PF AD - Departmento de Infectologia, Instituto Nacional de Ciencias Medicas y Nutricion "Salvador Zubiran". Vasco de Quiroga 15, Col. Seccion XVI, Del. Tlalpan. Mexico DF, Mexico. CP 14000. FAU - Lopez-Martinez, Alondra AU - Lopez-Martinez A AD - Departmento de Infectologia, Instituto Nacional de Ciencias Medicas y Nutricion "Salvador Zubiran". Vasco de Quiroga 15, Col. Seccion XVI, Del. Tlalpan. Mexico DF, Mexico. CP 14000. FAU - Pineirua-Menendez, Alicia AU - Pineirua-Menendez A AD - Departmento de Infectologia, Instituto Nacional de Ciencias Medicas y Nutricion "Salvador Zubiran". Vasco de Quiroga 15, Col. Seccion XVI, Del. Tlalpan. Mexico DF, Mexico. CP 14000. FAU - Montaner, Luis J AU - Montaner LJ AD - HIV-1 Immunopathogenesis Laboratory, The Wistar Institute. 3601 Spruce Street, Philadelphia, PA 19104. USA. FAU - Azzoni, Livio AU - Azzoni L AD - HIV-1 Immunopathogenesis Laboratory, The Wistar Institute. 3601 Spruce Street, Philadelphia, PA 19104. USA. FAU - Benitez, Cesar Rivera AU - Benitez CR AD - Servicio de Infectologia, Hospital General de Mexico, Dr. Balmis 148, Col. Doctores. Mexico DF, Mexico. CP 06726. FAU - Sereti, Irini AU - Sereti I AD - 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. FAU - Andrade-Villanueva, Jaime AU - Andrade-Villanueva J AD - Unidad de VIH, Hospital Civil de Guadalajara. Calle Hospital 278 S.H. Col. Alcalde Barranquitas. Guadalajara, Jalisco, Mexico. CP 44280. FAU - Mosqueda-Gomez, Juan L AU - Mosqueda-Gomez JL AD - Centro de Ambulatorio de Prevencion y Atencion en SIDA e Infecciones de Transmision Sexual Leon. Calle 20 de enero # 927, Col. Obregon. Leon, Guanajuato, Mexico CP 37000. FAU - Rodriguez, Benigno AU - Rodriguez B AD - Center for AIDS Research, Case Western Reserve University. 2061 Cornell Rd, Cleveland OH 44106. USA. FAU - Sanne, Ian AU - Sanne I AD - 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. FAU - Lederman, Michael M AU - Lederman MM AD - Center for AIDS Research, Case Western Reserve University. 2061 Cornell Rd, Cleveland OH 44106. USA. CN - CADIRIS study team LA - eng SI - ClinicalTrials.gov/NCT00988780 GR - Z99 AI999999/Intramural NIH HHS/United States PT - Journal Article PL - Netherlands TA - Lancet HIV JT - The lancet. HIV JID - 101645355 PMC - PMC4563882 MID - NIHMS717538 EDAT- 2015/09/15 06:00 MHDA- 2015/09/15 06:01 PMCR- 2015/09/09 CRDT- 2015/09/15 06:00 PHST- 2015/09/15 06:00 [entrez] PHST- 2015/09/15 06:00 [pubmed] PHST- 2015/09/15 06:01 [medline] PHST- 2015/09/09 00:00 [pmc-release] AID - 10.1016/S2352-3018(14)70027-X [doi] PST - ppublish SO - Lancet HIV. 2014 Nov 1;1(2):e60-e67. doi: 10.1016/S2352-3018(14)70027-X.