Research ArticleHIV

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

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Science Translational Medicine  03 Oct 2018:
Vol. 10, Issue 461, eaau4711
DOI: 10.1126/scitranslmed.aau4711

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Gut check for a promising HIV treatment

Eradicating HIV in infected patients likely requires disrupting the reservoir of infected T cells in the gastrointestinal tract. One way to accomplish this is by targeting cells expressing the α4β7, which has been tested in SIV models and is an approved therapy for inflammatory bowel disease. Uzzan and colleagues studied a small cohort of HIV-infected individuals on antiretroviral therapy that began anti-α4β7 treatment for their mild inflammatory bowel disease. The investigators performed colonoscopies before and several months after the anti-integrin treatment, allowing them to assess lymphoid populations and HIV prevalence before and after treatment. They saw that treatment disrupted local lymphoid aggregates and also affected peripheral immune populations. As with non–HIV-infected IBD patients, treatment was well tolerated. Their results are sure to draw interest from scientists and clinicians who believe targeting this integrin could possibly help cure HIV.

Abstract

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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