Use of a Small Molecule CCR5 Inhibitor in Macaques to Treat Simian Immunodeficiency Virus Infection or Prevent Simian-Human Immunodeficiency Virus Infection Academic Article uri icon

Overview

MeSH Major

  • Anti-Retroviral Agents
  • CCR5 Receptor Antagonists
  • Macaca mulatta
  • Pyrazoles
  • Simian Acquired Immunodeficiency Syndrome
  • Simian Immunodeficiency Virus
  • Valine

abstract

  • Human immunodeficiency virus type 1 (HIV-1) fuses with cells after sequential interactions between its envelope glycoproteins, CD4 and a coreceptor, usually CC chemokine receptor 5 (CCR5) or CXC receptor 4 (CXCR4). CMPD 167 is a CCR5-specific small molecule with potent antiviral activity in vitro. We show that CMPD 167 caused a rapid and substantial (4-200-fold) decrease in plasma viremia in six rhesus macaques chronically infected with simian immunodeficiency virus (SIV) strains SIVmac251 or SIVB670, but not in an animal infected with the X4 simian-human immunodeficiency virus (SHIV), SHIV-89.6P. In three of the SIV-infected animals, viremia reduction was sustained. In one, there was a rapid, but partial, rebound and in another, there was a rapid and complete rebound. There was a substantial delay (>21 d) between the end of therapy and the onset of full viremia rebound in two animals. We also evaluated whether vaginal administration of gel-formulated CMPD 167 could prevent vaginal transmission of the R5 virus, SHIV-162P4. Complete protection occurred in only 2 of 11 animals, but early viral replication was significantly less in the 11 CMPD 167-recipients than in 9 controls receiving carrier gel. These findings support the development of small molecule CCR5 inhibitors as antiviral therapies, and possibly as components of a topical microbicide to prevent HIV-1 sexual transmission.

publication date

  • November 17, 2003

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2194125

Digital Object Identifier (DOI)

  • 10.1084/jem.20031266

PubMed ID

  • 14623909

Additional Document Info

start page

  • 1551

end page

  • 62

volume

  • 198

number

  • 10