Vedolizumab Treatment in HIV-Infected Subjects Without Previous Antiretroviral Therapy

Summary

HIV cannot be eliminated and remains in the body despite the treatment that is used for HIV-infection called antiretroviral treatment (ART). Individuals undergoing ART interruption rapidly experience virus rebound in the blood. The current alternative therapeutic strategies to antiretroviral treatment have the aim to achieve the elimination of the virus in blood in the absence of ART. New drugs associated to ART that allow the elimination of the virus in the blood after ART withdrawn are needed. In monkeys infected with SIV, the analog of HIV, the virus has disappeared from the blood after administration of a compound and cessation of ART. There is an equivalent compound in humans called Vedolizumab. The aim of the present study is to research if Vedolizumab combined with ART, in subjects without previous ART, is able to eliminate the virus from the blood after ART is not taken.

Timeline

Start

2018-09

Primary completion

2020-05

Completion

2020-05

Publications

• Background Pernas M, Tarancon-Diez L, Rodriguez-Gallego E, Gomez J, Prado JG, Casado C, Dominguez-Molina B, Olivares I, Coiras M, Leon A, Rodriguez C, Benito JM, Rallon N, Plana M, Martinez-Madrid O, Dapena M, Iribarren JA, Del Romero J, Garcia F, Alcami J, Munoz-Fernandez M, Vidal F, Leal M, Lopez-Galindez C, Ruiz-Mateos E. Factors Leading to the Loss of Natural Elite Control of HIV-1 Infection. J Virol. 2018 Feb 12;92(5):e01805-17. doi: 10.1128/JVI.01805-17. Print 2018 Mar 1.
• Background Cicala C, Martinelli E, McNally JP, Goode DJ, Gopaul R, Hiatt J, Jelicic K, Kottilil S, Macleod K, O'Shea A, Patel N, Van Ryk D, Wei D, Pascuccio M, Yi L, McKinnon L, Izulla P, Kimani J, Kaul R, Fauci AS, Arthos J. The integrin alpha4beta7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1. Proc Natl Acad Sci U S A. 2009 Dec 8;106(49):20877-82. doi: 10.1073/pnas.0911796106. Epub 2009 Nov 20.
• Background Arthos J, Cicala C, Martinelli E, Macleod K, Van Ryk D, Wei D, Xiao Z, Veenstra TD, Conrad TP, Lempicki RA, McLaughlin S, Pascuccio M, Gopaul R, McNally J, Cruz CC, Censoplano N, Chung E, Reitano KN, Kottilil S, Goode DJ, Fauci AS. HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells. Nat Immunol. 2008 Mar;9(3):301-9. doi: 10.1038/ni1566. Epub 2008 Feb 10.
• Background Guzzo C, Ichikawa D, Park C, Phillips D, Liu Q, Zhang P, Kwon A, Miao H, Lu J, Rehm C, Arthos J, Cicala C, Cohen MS, Fauci AS, Kehrl JH, Lusso P. Virion incorporation of integrin alpha4beta7 facilitates HIV-1 infection and intestinal homing. Sci Immunol. 2017 May 12;2(11):eaam7341. doi: 10.1126/sciimmunol.aam7341.
• Background Byrareddy SN, Kallam B, Arthos J, Cicala C, Nawaz F, Hiatt J, Kersh EN, McNicholl JM, Hanson D, Reimann KA, Brameier M, Walter L, Rogers K, Mayne AE, Dunbar P, Villinger T, Little D, Parslow TG, Santangelo PJ, Villinger F, Fauci AS, Ansari AA. Targeting alpha4beta7 integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection. Nat Med. 2014 Dec;20(12):1397-400. doi: 10.1038/nm.3715. Epub 2014 Nov 24.
• Background Byrareddy SN, Arthos J, Cicala C, Villinger F, Ortiz KT, Little D, Sidell N, Kane MA, Yu J, Jones JW, Santangelo PJ, Zurla C, McKinnon LR, Arnold KB, Woody CE, Walter L, Roos C, Noll A, Van Ryk D, Jelicic K, Cimbro R, Gumber S, Reid MD, Adsay V, Amancha PK, Mayne AE, Parslow TG, Fauci AS, Ansari AA. Sustained virologic control in SIV+ macaques after antiretroviral and alpha4beta7 antibody therapy. Science. 2016 Oct 14;354(6309):197-202. doi: 10.1126/science.aag1276.
• Background Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, Van Assche G, Axler J, Kim HJ, Danese S, Fox I, Milch C, Sankoh S, Wyant T, Xu J, Parikh A; GEMINI 1 Study Group. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013 Aug 22;369(8):699-710. doi: 10.1056/NEJMoa1215734.
• Background Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S, Colombel JF, Sands BE, Lukas M, Fedorak RN, Lee S, Bressler B, Fox I, Rosario M, Sankoh S, Xu J, Stephens K, Milch C, Parikh A; GEMINI 2 Study Group. Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J Med. 2013 Aug 22;369(8):711-21. doi: 10.1056/NEJMoa1215739.
• Jimenez-Leon MR, Gasca-Capote C, Roca-Oporto C, Espinosa N, Sobrino S, Fontillon-Alberdi M, Gao C, Roseto I, Gladkov G, Rivas-Jeremias I, Neukam K, Sanchez-Hernandez JG, Rigo-Bonnin R, Cervera-Barajas AJ, Mesones R, Garcia F, Alvarez-Rios AI, Bachiller S, Vitalle J, Perez-Gomez A, Camacho-Sojo MI, Gallego I, Brander C, McGowan I, Mothe B, Viciana P, Yu X, Lichterfeld M, Lopez-Cortes LF, Ruiz-Mateos E. Vedolizumab and ART in recent HIV-1 infection unveil the role of alpha4beta7 in reservoir size. JCI Insight. 2024 Jul 9;9(16):e182312. doi: 10.1172/jci.insight.182312.

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