Anti-α4β7 therapy targets lymphoid aggregates in the gastrointestinal tract of HIV-1 infected individuals
Adam K Rosenstein,
Ivo N SahBandar,
Huaibin M Ko,
Michael J Corley,
Annalena La Porte,
Iliyan D Iliev,
Benjamin K Chen,
Timothy W Schacker,
Glaucia C. Furtado,
Jean K. Lim,
Luis J Montaner,
Lishomwa C Ndhlovu,
Lishomwa C. Ndhlovu
Posted 14 Jun 2018
bioRxiv DOI: 10.1101/346684 (published DOI: 10.1126/scitranslmed.aau4711)
Posted 14 Jun 2018
Herein, we present the first human study of anti-α4β7 therapy in a cohort of HIV-1 infected subjects with mild inflammatory bowel disease. α4β7+ gut homing CD4+ T cells 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 (Mab) have shown promise in preventing or attenuating the disease course of SIV in Non-Human Primate studies, the mechanisms of drug action remain elusive and the impact on HIV-1 persistence remains unanswered. 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 establishing and 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 continued evaluation of anti-α4β7 therapy in HIV-1 infection.
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