The Role of Integrin α4β7 in HIV Pathogenesis and Treatment

James Arthos, Claudia Cicala, Fatima Nawaz, Siddappa N. Byrareddy, Francois Villinger, Philip J. Santangelo, Aftab A. Ansari, Anthony S. Fauci

Research output: Contribution to journalReview article

12 Scopus citations

Abstract

Purpose of Review: Acute HIV infection is characterized by high-level viral replication throughout the body’s lymphoid system, particularly in gut-associated lymphoid tissues resulting in damage to structural components of gut tissue. This damage is irreversible and believed to contribute to the development of immune deficiencies. Antiretroviral therapy (ART) does not restore gut structure and function. Studies in macaques point to an alternative treatment strategy that may ameliorate gut damage. Integrin α4β7 mediates the homing of lymphocytes to gut tissues. Vedolizumab, a monoclonal antibody (mAb) antagonist of α4β7, has demonstrated efficacy and has been approved for the treatment of inflammatory bowel disease in humans. Here, we describe our current knowledge, and the gaps in our understanding, of the role of α4β7 in HIV pathogenesis and treatment. Recent Findings: When administered to macaques prior to infection, a nonhuman primate analogue of vedolizumab prevents transmission of SIV. In combination with ART, this mAb facilitates durable virologic control following treatment interruption. Summary: Targeting α4β7 represents a novel therapeutic approach to prevent and treat HIV infection.

Original languageEnglish (US)
Pages (from-to)127-135
Number of pages9
JournalCurrent HIV/AIDS Reports
Volume15
Issue number2
DOIs
StatePublished - Apr 1 2018

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Keywords

  • Antiretroviral therapy
  • GALT
  • HIV/SIV
  • Inflammatory bowel disease
  • Integrin αβ
  • Mucosal transmission

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Arthos, J., Cicala, C., Nawaz, F., Byrareddy, S. N., Villinger, F., Santangelo, P. J., Ansari, A. A., & Fauci, A. S. (2018). The Role of Integrin α4β7 in HIV Pathogenesis and Treatment. Current HIV/AIDS Reports, 15(2), 127-135. https://doi.org/10.1007/s11904-018-0382-3