Protection of rhesus macaques from vaginal infection by vaginally delivered maraviroc, an inhibitor of HIV-1 entry via the CCR5 co-receptor.

The Journal of Infectious Diseases
Ronald S VeazeyJohn P Moore

Abstract

An effective vaginal microbicide could reduce human immunodeficiency virus type 1 (HIV-1) transmission to women. Among microbicide candidates in clinical development is Maraviroc (MVC), a small-molecule drug that binds the CCR5 co-receptor and impedes HIV-1 entry into cells. Delivered systemically, MVC reduces viral load in HIV-1-infected individuals, but its ability to prevent transmission is untested. We have now evaluated MVC as a vaginal microbicide with use of a stringent model that involves challenge of rhesus macaques with a high-dose of a CCR5-using virus, SHIV-162P3. Gel-formulated, prescription-grade MVC provided dose-dependent protection, half-maximally at 0.5 mM (0.25 mg/mL). The duration of protection was transient; the longer the delay between MVC application and virus challenge, the less protection (half life of approximately 4 h). As expected, MVC neither protected against challenge with a CXCR4-using virus, SHIV-KU1, nor exacerbated postinfection viremia. These findings validate MVC development as a vaginal microbicide for women and should guide clinical programs.

References

Oct 1, 1996·Nature Medicine·P A MarxN J Alexander
May 20, 1997·AIDS Research and Human Retroviruses·S V JoagO Narayan
Jul 15, 1999·International Journal of Gynaecology and Obstetrics : the Official Organ of the International Federation of Gynaecology and Obstetrics·F R WitterC B Trapnell
Jun 11, 2005·Science·Thomas C Quinn, Julie Overbaugh
Mar 17, 2006·Nature Reviews. Microbiology·Leonid Margolis, Robin Shattock
Oct 5, 2006·Biotechnology & Genetic Engineering Reviews·Karl MalcolmDeborah Lowry
Sep 26, 2007·Annual Review of Medicine·Per Johan KlasseJohn P Moore
Jun 6, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Rodger D MacArthur, Richard M Novak
Jul 24, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ronald S VeazeyJohn P Moore
Jul 26, 2008·Science·Robert M GrantMark A Wainberg
Jan 20, 2009·Current HIV/AIDS Reports·Florian Hladik, Thomas J Hope
Feb 6, 2009·Journal of Virology·M-R AbrahamsUNKNOWN Center for HIV-AIDS Vaccine Immunology Consortium
Feb 6, 2009·The AAPS Journal·Lisa Cencia Rohan, Alexandra B Sassi
Apr 25, 2009·AIDS Research and Human Retroviruses·J RomanoM Mitchnick
Jan 6, 2010·Current Opinion in HIV and AIDS·Claudia Hawkins, Robert L Murphy

❮ Previous
Next ❯

Citations

Mar 23, 2011·Current HIV/AIDS Reports·Natasha A VermaMarla J Keller
Apr 6, 2011·Current HIV/AIDS Reports·Theodoros Kelesidis, Raphael J Landovitz
Apr 2, 2013·Antiviral Research·Aiman A Haqqani, John C Tilton
May 1, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Lee Adam WheelerJudy Lieberman
Jun 22, 2011·Proceedings of the National Academy of Sciences of the United States of America·Dennis R BurtonJohn P Moore
May 16, 2012·Proceedings of the National Academy of Sciences of the United States of America·Dan H BarouchJohn P Moore
Aug 31, 2012·AIDS Research and Human Retroviruses·Felix BroeckerKarin Moelling
Apr 26, 2013·AIDS Research and Human Retroviruses·Joseph RomanoUNKNOWN Antiretroviral Pharmacology In HIV Prevention Think Tank Participants
Sep 20, 2011·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Ming LiBharat Ramratnam
Feb 23, 2012·Cold Spring Harbor Perspectives in Medicine·Robin J Shattock, Zeda Rosenberg
Feb 15, 2012·Antimicrobial Agents and Chemotherapy·R Karl MalcolmJohn P Moore
Feb 25, 2011·European Journal of Medical Research·T Mertenskoetter, Paulina E Kaptur
Feb 22, 2012·HIV/AIDS : Research and Palliative Care·Adrian MajidBruce L Gilliam
Feb 9, 2012·The Indian Journal of Medical Research·UNKNOWN Nutan, Satish K Gupta
Nov 22, 2011·Future Medicinal Chemistry·Joanna S OlsenStephen Dewhurst
Aug 13, 2014·International Journal of Nanomedicine·Enrique Vacas-CórdobaM Ángeles Muñoz-Fernández
Jul 6, 2014·Science Translational Medicine·Amarendra PeguGary J Nabel
Nov 1, 2011·Annual Review of Medicine·Timothy J Wilkin, Roy M Gulick
Nov 14, 2014·Science Translational Medicine·Onofrio ZirafiJan Münch
Dec 3, 2014·Infectious Disease Clinics of North America·Amanda D CastelAlan E Greenberg
Jan 16, 2015·Science Translational Medicine·Chasity D AndrewsMartin Markowitz
Nov 1, 2012·The Journal of Antimicrobial Chemotherapy·R Karl MalcolmJohn P Moore
Jul 19, 2011·Drug Delivery and Translational Research·Jim A Turpin
Mar 19, 2014·Critical Reviews in Microbiology·George Panos, Dionysios Christos Watson
Feb 11, 2014·Expert Opinion on Drug Delivery·Osmond J D'Cruz, Fatih M Uckun
Oct 29, 2014·Expert Opinion on Drug Discovery·Katja Sliva
Mar 4, 2014·Journal of Pharmaceutical Sciences·Claire J ForbesR Karl Malcolm
Feb 2, 2016·Advanced Drug Delivery Reviews·R Karl MalcolmDiarmaid J Murphy
Apr 5, 2016·Materials Science & Engineering. C, Materials for Biological Applications·Cameron BallKim A Woodrow
Feb 4, 2016·Mucosal Immunology·R S VeazeyM M Lederman
Dec 30, 2015·AIDS Research and Human Retroviruses·Patricia FletcherRobin Shattock
Oct 19, 2013·Nanomedicine : Nanotechnology, Biology, and Medicine·Daniel Sepúlveda-CrespoM Ángeles Muñoz-Fernández
Dec 26, 2012·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Susan M FetherstonR Karl Malcolm
Aug 21, 2015·American Journal of Reproductive Immunology : AJRI·Whitney A NicholsAngela M Amedee
Jan 8, 2013·Current Opinion in Virology·Timothy J Henrich, Daniel R Kuritzkes
Oct 28, 2015·Protein Expression and Purification·Fabrice CeriniOliver Hartley

❮ Previous
Next ❯

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