Anti-α4β7 therapy targets lymphoid aggregates in the gastrointestinal tract of HIV-1-infected individuals

Sci Transl Med. 2018 Oct 3;10(461):eaau4711. doi: 10.1126/scitranslmed.aau4711.


Gut homing CD4+ T cells expressing the integrin α4β7 are early viral targets and contribute to HIV-1 pathogenesis, likely by seeding the gastrointestinal (GI) tract with HIV. Although simianized anti-α4β7 monoclonal antibodies have shown promise in preventing or attenuating the disease course of simian immunodeficiency virus in nonhuman primate studies, the mechanisms of drug action remain elusive. We present a cohort of individuals with mild inflammatory bowel disease and concomitant HIV-1 infection receiving anti-α4β7 treatment. By sampling the immune inductive and effector sites of the GI tract, we have discovered that anti-α4β7 therapy led to a significant and unexpected attenuation of lymphoid aggregates, most notably in the terminal ileum. Given that lymphoid aggregates serve as important sanctuary sites for maintaining viral reservoirs, their attrition by anti-α4β7 therapy has important implications for HIV-1 therapeutics and eradication efforts and defines a rational basis for the use of anti-α4β7 therapy in HIV-1 infection.

Publication types

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

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • B-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • Female
  • Gastrointestinal Tract / pathology*
  • Gastrointestinal Tract / virology*
  • HIV Infections / blood
  • HIV Infections / immunology
  • HIV Infections / therapy*
  • Humans
  • Integrins / antagonists & inhibitors*
  • Integrins / metabolism
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Lymphocyte Subsets / drug effects
  • Lymphocyte Subsets / immunology
  • Lymphoid Tissue / pathology*
  • Male
  • Middle Aged
  • RNA Splicing / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • Antibodies, Monoclonal, Humanized
  • Integrins
  • RNA, Messenger
  • integrin alpha4beta7
  • vedolizumab