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  • 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.

     

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Centre for the AIDS Programme of Research in South Africa

CAPRISA was created in 2001 and formally established in 2002 under the NIH-funded Comprehensive International Program of Research on AIDS (CIPRA) by five partner institutions; University of KwaZulu-Natal, University of Cape Town, University of Western Cape, National Institute for Communicable Diseases, and Columbia University in New York. CAPRISA is a designated UNAIDS Collaborating Centre for HIV Prevention Research. The main goal of CAPRISA is to undertake globally relevant and locally responsive research that contributes to understanding HIV pathogenesis, prevention and epidemiology as well as the links between tuberculosis and AIDS care.