In vitro inhibition of HIV-1 by Met-SDF-1beta alone or in combination with antiretroviral drugs

Antivir Ther. 2000 Sep;5(3):199-204.

Abstract

Compounds that can block the CXCR4 chemokine receptor are a promising new class of antiretroviral agents. In these experiments we studied the effect of a modified form of the native stromal cell-derived factor-1 (SDF-1), Met-SDF-1beta. The in vitro susceptibility of two different CXCR4-tropic HIV-1 strains was determined. Antiviral effect was assessed by the reduction of p24 antigen production in PHA-stimulated peripheral blood mononuclear cells with exposure to the modified SDF-1 molecule. The 50% inhibitory concentrations (IC50) were derived from six separate experiments. The IC50 against the two HIV-1 isolates was in 1.0-2.8 microg/ml range for Met-SDF-1beta. Met-SDF-1beta showed synergy to additivity with either zidovudine or nelfinavir at IC75 IC90 and IC95. Additivity was seen when Met-SDF-1beta was combined with efavirenz. No cellular toxicity was observed at the highest concentrations when these agents were used either singly or in combination. This compound is a promising new candidate in a receptor-based approach to HIV-1 infection in conjunction with currently available combination antiretroviral drug therapies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Chemokine CXCL12
  • Chemokines, CXC / pharmacology*
  • Drug Interactions
  • Drug Therapy, Combination
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • Humans
  • Leukocytes, Mononuclear / virology
  • Methionine / analogs & derivatives*
  • Methionine / pharmacology*
  • Nelfinavir / pharmacology
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Zidovudine / pharmacology*

Substances

  • Anti-HIV Agents
  • Chemokine CXCL12
  • Chemokines, CXC
  • Reverse Transcriptase Inhibitors
  • methionine stromal cell-derived factor-1beta
  • Zidovudine
  • Methionine
  • Nelfinavir