Sustained virologic control in SIV+ macaques after antiretroviral and alpha(4)beta(7) antibody therapy

• Type of Material: Article
• Authors: Siddappa Byrareddy, Emory University; James Arthos, National Institutes of Health; Claudia Cicala, National Institutes of Health; Francois Villinger, Emory University; Kristina T. Ortiz, Emory University; Dawn Little, Emory University; Neil Sidell, Emory University; Maureen A. Kane, University of Maryland; Jianshi Yu, University of Maryland; Jace W. Jones, University of Maryland; Philip J. Santangelo, Emory University; Chiara Zurla, Emory University; Lyle R. McKinnon, Centre for the AIDS Program of Research in South Africa (CAPRISA); Kelly B. Arnold, University of Michigan; Caroline E. Woody, University of Michigan; Lutz Walter, Leibniz Institute for Primate Research; Christian Roos, Leibniz Institute for Primate Research; Angela Noll, Leibniz Institute for Primate Research; Donald Van Ryk, NIH; Katija Jelicic, NIH; Raffaello Cimbro, Johns Hopkins School of Medicine; Sanjeev Gumbar, Emory University; Michelle Dian Reid, Emory University; Volkan Adsay, Emory University; Praveen K. Amancha, Emory University; Ann E. Mayne, affiliation; Tristram G Parslow, Emory University; Anthony S. Fauci, NIH; Aftab A Ansari, Emory University
• Language: English
• Date: 2016-10-14
• Publisher: American Association for the Advancement of Science
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016, American Association for the Advancement of Science. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1126/science.aag1276
• Title of Journal or Parent Work: Science
• ISSN: 0036-8075
• Volume: 354
• Issue: 6309
• Start Page: 197
• End Page: 202
• Grant/Funding Information: Additional support was provided by the University of Maryland School of Pharmacy Mass Spectrometry Center (SOP1841-1QB2014). J.A., C.C., and A.S.F. are investors in the patent and patent application 20160075786 submitted by the NIAID.; The work performed herein was supported by NIAID-NIH R01 AI098628, R01 AI111907, R01 HD077260, U.S. Food and Drug Administration U01FD005266, the Intramural Program of the NIAID, NIH, Bethesda, MD, and the base grant to the Yerkes National Primate Research Center of Emory University NIH-ORIP-OD-51OD-11132.
• Keywords: LYMPHOID-TISSUE; SIMIAN IMMUNODEFICIENCY VIRUS; EXPRESSION; TYPE-1 INFECTION; SIVMAC251 ACQUISITION; HIV; RETINOIC ACID; Multidisciplinary Sciences; Science & Technology; SIGNATURES; Science & Technology - Other Topics; REPLICATION; T-CELL DEPLETION
• Research Categories: Biology, Microbiology; Biology, Virology; Health Sciences, Immunology

Abstract

Antiretroviral drug therapy (ART) effectively suppresses replication of both the immunodeficiency viruses, human (HIV) and simian (SIV); however, virus rebounds soon after ART is withdrawn. SIV-infected monkeys were treated with a 90-day course of ART initiated at 5 weeks post infection followed at 9 weeks post infection by infusions of a primatized monoclonal antibody against the α 4 β 7 integrin administered every 3 weeks until week 32. These animals subsequently maintained low to undetectable viral loads and normal CD4 + T cell counts in plasma and gastrointestinal tissues for more than 9 months, even after all treatment was withdrawn. This combination therapy allows macaques to effectively control viremia and reconstitute their immune systems without a need for further therapy.