October 3, 2018

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

Mathieu Uzzan, Minami Tokuyama, Adam K. Rosenstein, Costin Tomescu, Ivo N. SahBandar, Huaibin M. Ko, Louise Leyre, Anupa Chokola, Emma Kaplan-Lewis, Gabriela Rodriguez, Akihiro Seki, Michael J. Corley, Judith Aberg, Annalena La Porte, Eun-young Park, Hideki Ueno, Ioannis Oikonomou, Itai Doron, Iliyan D. Iliev, Benjamin K. Chen, Jennifer Lui, Timothy W. Schacker, Glaucia C. Furtado, Sergio A. Lira, Jean-Frederic Colombel, Amir Horowitz, Jean K. Lim, Nicolas Chomont, Adeeb H. Rahman, Luis J. Montaner, Lishomwa C. Ndhlovu, and Saurabh Mehandru

Science Translational Medicine

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.

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