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

TitleAnti-α4β7 therapy targets lymphoid aggregates in the gastrointestinal tract of HIV-1-infected individuals.
Publication TypeJournal Article
Year of Publication2018
AuthorsUzzan M, Tokuyama M, Rosenstein AK, Tomescu C, SahBandar IN, Ko HM, Leyre L, Chokola A, Kaplan-Lewis E, Rodriguez G, Seki A, Corley MJ, Aberg J, La Porte A, Park E-Y, Ueno H, Oikonomou I, Doron I, Iliev ID, Chen BK, Lui J, Schacker TW, Furtado GC, Lira SA, Colombel J-F, Horowitz A, Lim JK, Chomont N, Rahman AH, Montaner LJ, Ndhlovu LC, Mehandru S
JournalSci Transl Med
Volume10
Issue461
Date Published2018 Oct 03
ISSN1946-6242
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.

DOI10.1126/scitranslmed.aau4711
Alternate JournalSci Transl Med
PubMed ID30282696
Grant ListR01 DK112296 / DK / NIDDK NIH HHS / United States