Maraviroc (CCR5) Antagonism to Decrease the Incidence of the Immune Reconstitution Inflammatory Syndrome in HIV-Infected Patients

Summary

The purpose of this study is to determine if Maraviroc administration can decrease IRIS incidence in HIV infected patients initiating ARV therapy.

Timeline

Start

2009-12

Primary completion

2013-03

Completion

2013-04

Publications

• Background Jensen-Fangel S, Pedersen L, Pedersen C, Larsen CS, Tauris P, Moller A, Sorensen HT, Obel N. Low mortality in HIV-infected patients starting highly active antiretroviral therapy: a comparison with the general population. AIDS. 2004 Jan 2;18(1):89-97. doi: 10.1097/00002030-200401020-00011.
• Background Corey DM, Kim HW, Salazar R, Illescas R, Villena J, Gutierrez L, Sanchez J, Tabet SR. Brief report: effectiveness of combination antiretroviral therapy on survival and opportunistic infections in a developing world setting: an observational cohort study. J Acquir Immune Defic Syndr. 2007 Apr 1;44(4):451-5. doi: 10.1097/QAI.0b013e31802f8512.
• Background Lederman MM. Immune restoration and CD4+ T-cell function with antiretroviral therapies. AIDS. 2001 Feb;15 Suppl 2:S11-5. doi: 10.1097/00002030-200102002-00003.
• Background Lawn SD, Myer L, Bekker LG, Wood R. CD4 cell count recovery among HIV-infected patients with very advanced immunodeficiency commencing antiretroviral treatment in sub-Saharan Africa. BMC Infect Dis. 2006 Mar 21;6:59. doi: 10.1186/1471-2334-6-59.
• Background Battegay M, Nuesch R, Hirschel B, Kaufmann GR. Immunological recovery and antiretroviral therapy in HIV-1 infection. Lancet Infect Dis. 2006 May;6(5):280-7. doi: 10.1016/S1473-3099(06)70463-7.
• Background Murdoch DM, Venter WD, Van Rie A, Feldman C. Immune reconstitution inflammatory syndrome (IRIS): review of common infectious manifestations and treatment options. AIDS Res Ther. 2007 May 8;4:9. doi: 10.1186/1742-6405-4-9.
• Background Autran B, Carcelain G, Li TS, Blanc C, Mathez D, Tubiana R, Katlama C, Debre P, Leibowitch J. Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science. 1997 Jul 4;277(5322):112-6. doi: 10.1126/science.277.5322.112.
• Background Shelburne SA, Visnegarwala F, Darcourt J, Graviss EA, Giordano TP, White AC Jr, Hamill RJ. Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy. AIDS. 2005 Mar 4;19(4):399-406. doi: 10.1097/01.aids.0000161769.06158.8a.
• Background Lederman MM, Penn-Nicholson A, Cho M, Mosier D. Biology of CCR5 and its role in HIV infection and treatment. JAMA. 2006 Aug 16;296(7):815-26. doi: 10.1001/jama.296.7.815.
• Background Westby M, van der Ryst E. CCR5 antagonists: host-targeted antivirals for the treatment of HIV infection. Antivir Chem Chemother. 2005;16(6):339-54. doi: 10.1177/095632020501600601.
• Background Knobel H, Alonso J, Casado JL, Collazos J, Gonzalez J, Ruiz I, Kindelan JM, Carmona A, Juega J, Ocampo A; GEEMA Study Group. Validation of a simplified medication adherence questionnaire in a large cohort of HIV-infected patients: the GEEMA Study. AIDS. 2002 Mar 8;16(4):605-13. doi: 10.1097/00002030-200203080-00012.
• Background French MA, Lenzo N, John M, Mallal SA, McKinnon EJ, James IR, Price P, Flexman JP, Tay-Kearney ML. Immune restoration disease after the treatment of immunodeficient HIV-infected patients with highly active antiretroviral therapy. HIV Med. 2000 Mar;1(2):107-15. doi: 10.1046/j.1468-1293.2000.00012.x.
• Background Jevtovic DJ, Salemovic D, Ranin J, Pesic I, Zerjav S, Djurkovic-Djakovic O. The prevalence and risk of immune restoration disease in HIV-infected patients treated with highly active antiretroviral therapy. HIV Med. 2005 Mar;6(2):140-3. doi: 10.1111/j.1468-1293.2005.00277.x.
• Background French MA, Price P, Stone SF. Immune restoration disease after antiretroviral therapy. AIDS. 2004 Aug 20;18(12):1615-27. doi: 10.1097/01.aids.0000131375.21070.06.
• Background Singh N, Perfect JR. Immune reconstitution syndrome associated with opportunistic mycoses. Lancet Infect Dis. 2007 Jun;7(6):395-401. doi: 10.1016/S1473-3099(07)70085-3.
• Background Bonnet MM, Pinoges LL, Varaine FF, Oberhauser BB, O'Brien DD, Kebede YY, Hewison CC, Zachariah RR, Ferradini LL. Tuberculosis after HAART initiation in HIV-positive patients from five countries with a high tuberculosis burden. AIDS. 2006 Jun 12;20(9):1275-9. doi: 10.1097/01.aids.0000232235.26630.ee.
• Background Rodriguez-Rosado R, Soriano V, Dona C, Gonzalez-Lahoz J. Opportunistic infections shortly after beginning highly active antiretroviral therapy. Antivir Ther. 1998;3(4):229-31.
• Background Lortholary O, Fontanet A, Memain N, Martin A, Sitbon K, Dromer F; French Cryptococcosis Study Group. Incidence and risk factors of immune reconstitution inflammatory syndrome complicating HIV-associated cryptococcosis in France. AIDS. 2005 Jul 1;19(10):1043-9. doi: 10.1097/01.aids.0000174450.70874.30.
• Background Michelet C, Arvieux C, Francois C, Besnier JM, Rogez JP, Breux JP, Souala F, Allavena C, Raffi F, Garre M, Cartier F. Opportunistic infections occurring during highly active antiretroviral treatment. AIDS. 1998 Oct 1;12(14):1815-22. doi: 10.1097/00002030-199814000-00013.
• Background Park WB, Choe PG, Jo JH, Kim SH, Bang JH, Kim HB, Kim NJ, Oh MD, Choe KW. Tuberculosis manifested by immune reconstitution inflammatory syndrome during HAART. AIDS. 2007 Apr 23;21(7):875-7. doi: 10.1097/QAD.0b013e3280f7751f.
• Background Domingo P, Torres OH, Ris J, Vazquez G. Herpes zoster as an immune reconstitution disease after initiation of combination antiretroviral therapy in patients with human immunodeficiency virus type-1 infection. Am J Med. 2001 Jun 1;110(8):605-9. doi: 10.1016/s0002-9343(01)00703-3.
• Background Manosuthi W, Kiertiburanakul S, Phoorisri T, Sungkanuparph S. Immune reconstitution inflammatory syndrome of tuberculosis among HIV-infected patients receiving antituberculous and antiretroviral therapy. J Infect. 2006 Dec;53(6):357-63. doi: 10.1016/j.jinf.2006.01.002. Epub 2006 Feb 17.
• Background Madec Y, Laureillard D, Pinoges L, Fernandez M, Prak N, Ngeth C, Moeung S, Song S, Balkan S, Ferradini L, Quillet C, Fontanet A. Response to highly active antiretroviral therapy among severely immuno-compromised HIV-infected patients in Cambodia. AIDS. 2007 Jan 30;21(3):351-9. doi: 10.1097/QAD.0b013e328012c54f.
• Background Braitstein P, Brinkhof MW, Dabis F, Schechter M, Boulle A, Miotti P, Wood R, Laurent C, Sprinz E, Seyler C, Bangsberg DR, Balestre E, Sterne JA, May M, Egger M; Antiretroviral Therapy in Lower Income Countries (ART-LINC) Collaboration; ART Cohort Collaboration (ART-CC) groups. Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries. Lancet. 2006 Mar 11;367(9513):817-24. doi: 10.1016/S0140-6736(06)68337-2.
• Background Zachariah R, Fitzgerald M, Massaquoi M, Pasulani O, Arnould L, Makombe S, Harries AD. Risk factors for high early mortality in patients on antiretroviral treatment in a rural district of Malawi. AIDS. 2006 Nov 28;20(18):2355-60. doi: 10.1097/QAD.0b013e32801086b0.
• Background Sabin CA, Smith CJ, Gumley H, Murphy G, Lampe FC, Phillips AN, Prinz B, Youle M, Johnson MA. Late presenters in the era of highly active antiretroviral therapy: uptake of and responses to antiretroviral therapy. AIDS. 2004 Nov 5;18(16):2145-51. doi: 10.1097/00002030-200411050-00006.
• Background Manabe YC, Campbell JD, Sydnor E, Moore RD. Immune reconstitution inflammatory syndrome: risk factors and treatment implications. J Acquir Immune Defic Syndr. 2007 Dec 1;46(4):456-62. doi: 10.1097/qai.0b013e3181594c8c.
• Background Lawn SD, Myer L, Bekker LG, Wood R. Tuberculosis-associated immune reconstitution disease: incidence, risk factors and impact in an antiretroviral treatment service in South Africa. AIDS. 2007 Jan 30;21(3):335-41. doi: 10.1097/QAD.0b013e328011efac.
• Background Delves PJ, Roitt IM. The immune system. First of two parts. N Engl J Med. 2000 Jul 6;343(1):37-49. doi: 10.1056/NEJM200007063430107. No abstract available.
• Background Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998 Mar 26;338(13):853-60. doi: 10.1056/NEJM199803263381301.
• Background Egger M, Hirschel B, Francioli P, Sudre P, Wirz M, Flepp M, Rickenbach M, Malinverni R, Vernazza P, Battegay M. Impact of new antiretroviral combination therapies in HIV infected patients in Switzerland: prospective multicentre study. Swiss HIV Cohort Study. BMJ. 1997 Nov 8;315(7117):1194-9. doi: 10.1136/bmj.315.7117.1194.
• Background O'Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics. 1979 Sep;35(3):549-56.
• Background Storey JD, Tibshirani R. Statistical significance for genomewide studies. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9440-5. doi: 10.1073/pnas.1530509100. Epub 2003 Jul 25.
• Background Lederman MM, Margolis L. The lymph node in HIV pathogenesis. Semin Immunol. 2008 Jun;20(3):187-95. doi: 10.1016/j.smim.2008.06.001. Epub 2008 Jul 14.
• Background Sieg SF, Bazdar DA, Lederman MM. S-phase entry leads to cell death in circulating T cells from HIV-infected persons. J Leukoc Biol. 2008 Jun;83(6):1382-7. doi: 10.1189/jlb.0907643. Epub 2008 Mar 27.
• Background Sieg SF, Rodriguez B, Asaad R, Jiang W, Bazdar DA, Lederman MM. Peripheral S-phase T cells in HIV disease have a central memory phenotype and rarely have evidence of recent T cell receptor engagement. J Infect Dis. 2005 Jul 1;192(1):62-70. doi: 10.1086/430620. Epub 2005 May 26.
• Background Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, Kazzaz Z, Bornstein E, Lambotte O, Altmann D, Blazar BR, Rodriguez B, Teixeira-Johnson L, Landay A, Martin JN, Hecht FM, Picker LJ, Lederman MM, Deeks SG, Douek DC. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006 Dec;12(12):1365-71. doi: 10.1038/nm1511. Epub 2006 Nov 19.
• Background Jiang W, Lederman MM, Hunt P, Sieg SF, Haley K, Rodriguez B, Landay A, Martin J, Sinclair E, Asher AI, Deeks SG, Douek DC, Brenchley JM. Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection. J Infect Dis. 2009 Apr 15;199(8):1177-85. doi: 10.1086/597476.
• Background Funderburg N, Luciano AA, Jiang W, Rodriguez B, Sieg SF, Lederman MM. Toll-like receptor ligands induce human T cell activation and death, a model for HIV pathogenesis. PLoS One. 2008 Apr 2;3(4):e1915. doi: 10.1371/journal.pone.0001915.
• Background Pandrea I, Apetrei C, Gordon S, Barbercheck J, Dufour J, Bohm R, Sumpter B, Roques P, Marx PA, Hirsch VM, Kaur A, Lackner AA, Veazey RS, Silvestri G. Paucity of CD4+CCR5+ T cells is a typical feature of natural SIV hosts. Blood. 2007 Feb 1;109(3):1069-76. doi: 10.1182/blood-2006-05-024364. Epub 2006 Sep 26.
• Background Bourgarit A, Carcelain G, Martinez V, Lascoux C, Delcey V, Gicquel B, Vicaut E, Lagrange PH, Sereni D, Autran B. Explosion of tuberculin-specific Th1-responses induces immune restoration syndrome in tuberculosis and HIV co-infected patients. AIDS. 2006 Jan 9;20(2):F1-7. doi: 10.1097/01.aids.0000202648.18526.bf.
• Background Salkowitz JR, Sieg SF, Harding CV, Lederman MM. In vitro human memory CD8 T cell expansion in response to cytomegalovirus requires CD4+ T cell help. J Infect Dis. 2004 Mar 15;189(6):971-83. doi: 10.1086/382032. Epub 2004 Mar 1.
• Background Ratnam I, Chiu C, Kandala NB, Easterbrook PJ. Incidence and risk factors for immune reconstitution inflammatory syndrome in an ethnically diverse HIV type 1-infected cohort. Clin Infect Dis. 2006 Feb 1;42(3):418-27. doi: 10.1086/499356. Epub 2005 Dec 28.
• Araujo-Pereira M, Barreto-Duarte B, Arriaga MB, Musselwhite LW, Vinhaes CL, Belaunzaran-Zamudio PF, Rupert A, Montaner LJ, Lederman MM, Sereti I, Madero JGS, Andrade BB. Relationship Between Anemia and Systemic Inflammation in People Living With HIV and Tuberculosis: A Sub-Analysis of the CADIRIS Clinical Trial. Front Immunol. 2022 Jun 23;13:916216. doi: 10.3389/fimmu.2022.916216. eCollection 2022.
• Sierra-Madero JG, Ellenberg SS, Rassool MS, Tierney A, Belaunzaran-Zamudio PF, Lopez-Martinez A, Pineirua-Menendez A, Montaner LJ, Azzoni L, Benitez CR, Sereti I, Andrade-Villanueva J, Mosqueda-Gomez JL, Rodriguez B, Sanne I, Lederman MM; CADIRIS study team. Effect of the CCR5 antagonist maraviroc on the occurrence of immune reconstitution inflammatory syndrome in HIV (CADIRIS): a double-blind, randomised, placebo-controlled trial. Lancet HIV. 2014 Nov;1(2):e60-7. doi: 10.1016/S2352-3018(14)70027-X. Epub 2014 Oct 21.
• Sierra-Madero JG, Ellenberg S, Rassool MS, Tierney A, Belaunzaran-Zamudio PF, Lopez-Martinez A, Pineirua-Menendez A, Montaner LJ, Azzoni L, Benitez CR, Sereti I, Andrade-Villanueva J, Mosqueda-Gomez JL, Rodriguez B, Sanne I, Lederman MM; CADIRIS study team. 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. Lancet HIV. 2014 Nov 1;1(2):e60-e67. doi: 10.1016/S2352-3018(14)70027-X.

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Indications