Sustained virologic control in SIV+ macaques after antiretroviral and α4β7 antibody therapy

Science. 2016 Oct 14;354(6309):197-202. doi: 10.1126/science.aag1276.

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of both the immunodeficiency viruses, human (HIV) and simian (SIV); however, virus rebounds soon after ART is withdrawn.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 α4β7 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normal CD4+ T cell counts in plasma and gastrointestinal tissues for more than 9 months, even after all treatment was withdrawn.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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology
  • Combined Modality Therapy
  • Cytokines / blood
  • Disease Models, Animal
  • Female
  • Gastrointestinal Tract / immunology
  • Immunization, Passive / methods*
  • Infusions, Intravenous
  • Integrin alpha4 / immunology*
  • Integrin beta Chains / immunology*
  • Killer Cells, Natural / immunology
  • Macaca mulatta
  • Male
  • Membrane Glycoproteins / immunology
  • Simian Acquired Immunodeficiency Syndrome / blood
  • Simian Acquired Immunodeficiency Syndrome / drug therapy
  • Simian Acquired Immunodeficiency Syndrome / therapy*
  • Simian Acquired Immunodeficiency Syndrome / virology*
  • Simian Immunodeficiency Virus / immunology*
  • Simian Immunodeficiency Virus / isolation & purification
  • T-Lymphocyte Subsets / immunology
  • Tretinoin / blood
  • Viral Envelope Proteins / immunology
  • Viral Load / immunology
  • Viremia / blood
  • Viremia / drug therapy
  • Viremia / therapy*
  • Viremia / virology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Cytokines
  • Integrin beta Chains
  • Membrane Glycoproteins
  • Viral Envelope Proteins
  • gp120 protein, Simian immunodeficiency virus
  • integrin beta7
  • Integrin alpha4
  • Tretinoin
  • vedolizumab