Integrin α4β7 expression on peripheral blood CD4+ T cells predicts HIV acquisition and disease progression
In the January 24th issue of Science Translation Medicine, CAPRISA researchers Dr. Aida Sivro and Dr. Lyle McKinnon led a study that demonstrated that pre-HIV infection levels of α4β7 expression on peripheral blood CD4+ T cells was associated with an increase in rates of HIV acquisition in women from the CAPRISA 004 trial of tenofovir 1% gel.
This association was independent of T cell memory and activation phenotypes and concomitant genital inflammation. Infection by HIV strains containing V2 Env motifs with a preference for α4β7 binding was increased in women with higher α4β7 expression.
In addition to its relationship to acquisition, pre-HIV levels of α4β7 expression on peripheral CD4+ T cells predicted a more rapid rate of HIV disease progression, correlating with set point viral load and a >2 fold increased rate of CD4 decline. Increased frequencies of α4β7 CD4+ T cells pre-HIV infection were also associated with higher expression of LPS binding protein (LBP), a microbial translocation marker, for up to 3 years post-infection.
These findings suggest that there is a link between gut homing potential, gut mucosal damage, and more rapid disease progression. At the earliest stages of HIV infection CD4+ T cells expressing α4β7 were rapidly depleted, particularly from the GI tract, and were not restored by early antiretroviral therapy (ART). This study is the first to link the pre-HIV α4β7 expression with HIV clinical outcomes in humans, supporting the previous observations made in animal models.
Given the availability of a clinically approved anti-α4β7 monoclonal antibody (called Vedolizumab) for treatment of inflammatory bowel disease (IBD), these results suggest that targeting of α4β7 can be readily evaluated as a clinical intervention for HIV prevention and/or treatment.
For further reading
A Sivro et al. Integrin α4β7 expression on peripheral blood CD4+ T cells predicts HIV acquisition and disease progression outcomes. Science Translational Medicine 2018; 10(425): eaam6354 DOI: 10.1126/scitranslmed.aam6354.