Effect of a CCR5 inhibitor on viral loads in macaques dual-infected with R5 and X4 primate immunodeficiency viruses

Virology
S M WolinskyJ P Moore

Abstract

Human immunodeficiency virus type 1 (HIV-1) fusion with its target cells is initiated by sequential interactions between its envelope glycoprotein, CD4, and a co-receptor, usually CCR5 or CXCR4. Small molecules that bind to CCR5 and prevent its use by R5 HIV-1 strains are now being developed clinically as antiviral drugs. To test whether a block to CCR5 promotes the replication of viruses that enter cells via CXCR4 and are associated with accelerated disease progression, we administered a small molecule CCR5 inhibitor, CMPD 167, to three macaques dual-infected with both R5 (SIVmac251) and X4 (SHIV-89.6P) viruses. CMPD 167 caused a rapid and substantial (on average, 50-fold) suppression of R5 virus replication in each animal. In two of the animals, but not in the third, a rapid, transient, 8- to 15-fold increase in the amount of plasma X4 virus occurred. In neither animal was the increase in X4 viral load sustained throughout therapy, however. These observations may have relevance for the development of CCR5 inhibitors for treatment of HIV-1 infection of humans.

References

May 1, 1994·The Journal of Infectious Diseases·D D Richman, S A Bozzette
Jul 1, 1996·AIDS Research and Human Retroviruses·S R LewinS M Crowe
Sep 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·A KinterA S Fauci
Jun 8, 1999·Annual Review of Immunology·E A BergerJ M Farber
Feb 22, 2001·The Journal of Clinical Investigation·S PhilpottH Burger
Jun 14, 2001·AIDS·R W Doms
Oct 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·J M StrizkiB M Baroudy
Jan 10, 2002·Proceedings of the National Academy of Sciences of the United States of America·Alexandra TrkolaJohn P Moore
Jul 18, 2002·Nature Reviews. Drug Discovery·Matthias K Schwarz, Timothy N C Wells
Jul 19, 2002·The Journal of General Virology·Paul R Clapham, Aine McKnight
May 30, 2003·The New England Journal of Medicine·J Michael Kilby, Joseph J Eron
Sep 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·John P Moore, Robert W Doms
Sep 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·Janet M HarouseCecilia Cheng-Mayer

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Citations

Jun 20, 2014·PLoS Computational Biology·Borislav SavkovicJohn M Murray
Aug 15, 2009·PLoS Computational Biology·Ariel D WeinbergerLeor S Weinberger
Jun 3, 2011·Mathematical Biosciences and Engineering : MBE·Ariel D Weinberger, Alan S Perelson
Sep 24, 2010·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Anne-Laure FiserPierre Corbeau
Oct 17, 2007·Annual Review of Pharmacology and Toxicology·Shawn E Kuhmann, Oliver Hartley
Sep 1, 2006·Current Opinion in HIV and AIDS·Masanori Baba
Sep 9, 2006·Annual Review of Medicine·Athe M N Tsibris, Daniel R Kuritzkes
Sep 3, 2009·AIDS·Pierre Corbeau, Jacques Reynes
Jan 24, 2007·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Timothy J WilkinRoy M Gulick
Jul 23, 2009·Antiviral Research·Koen K A Van Rompay
Sep 19, 2006·Seminars in Immunology·Fernando Arenzana-Seisdedos, Marc Parmentier
Dec 7, 2005·Antiviral Chemistry & Chemotherapy·Mike Westby, Elna van der Ryst
Sep 10, 2011·AIDS Research and Human Retroviruses·Koen K A Van Rompay
Feb 10, 2011·Journal of Translational Medicine·Lucia Lopalco
Oct 13, 2005·Journal of Biomolecular Structure & Dynamics·A M Andrianov
Jun 25, 2005·The Journal of Biological Chemistry·Hana GoldingAlan Sher
Aug 7, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Carsten SchröderJulie A DeMartino
Feb 16, 2012·Bioorganicheskaia khimiia·E O BaranovaV I Shvets
Mar 1, 2010·Antibiotiques : Journal Des Agent Anti-infectieux·K C PsomasJ Reynes

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