title: Interleukin-21 combined with ART reduces inflammation and viral reservoir in SIV-infected macaques.
abstract: Despite successful control of viremia, many HIV-infected individuals given antiretroviral therapy (ART) exhibit residual inflammation, which is associated with non-AIDS-related morbidity and mortality and may contribute to virus persistence during ART. Here, we investigated the effects of IL-21 administration on both inflammation and virus persistence in ART-treated, SIV-infected rhesus macaques (RMs). Compared with SIV-infected animals only given ART, SIV-infected RMs given both ART and IL-21 showed improved restoration of intestinal Th17 and Th22 cells and a more effective reduction of immune activation in blood and intestinal mucosa, with the latter maintained through 8 months after ART interruption. Additionally, IL-21, in combination with ART, was associated with reduced levels of SIV RNA in plasma and decreased CD4(+) T cell levels harboring replication-competent virus during ART. At the latest experimental time points, which were up to 8 months after ART interruption, plasma viremia and cell-associated SIV DNA levels remained substantially lower than those before ART initiation in IL-21-treated animals but not in controls. Together, these data suggest that IL-21 supplementation of ART reduces residual inflammation and virus persistence in a relevant model of lentiviral disease and warrants further investigation as a potential intervention for HIV infection.
authors.forename: Luca
authors.initials: L
authors.lastname: Micci
authors.forename: Emily S
authors.initials: ES
authors.lastname: Ryan
authors.forename: Rémi
authors.initials: R
authors.lastname: Fromentin
authors.forename: Steven E
authors.initials: SE
authors.lastname: Bosinger
authors.forename: Justin L
authors.initials: JL
authors.lastname: Harper
authors.forename: Tianyu
authors.initials: T
authors.lastname: He
authors.forename: Sara
authors.initials: S
authors.lastname: Paganini
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Easley
authors.forename: Ann
authors.initials: A
authors.lastname: Chahroudi
authors.forename: Clarisse
authors.initials: C
authors.lastname: Benne
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Gumber
authors.forename: Colleen S
authors.initials: CS
authors.lastname: McGary
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Rogers
authors.forename: Claire
authors.initials: C
authors.lastname: Deleage
authors.forename: Carissa
authors.initials: C
authors.lastname: Lucero
authors.forename: Siddappa N
authors.initials: SN
authors.lastname: Byrareddy
authors.forename: Cristian
authors.initials: C
authors.lastname: Apetrei
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chomont
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
authors.forename: Mirko
authors.initials: M
authors.lastname: Paiardini
mesh_terms: D000818:Animals; D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D004279:DNA, Viral / Q000097:blood / Q000276:immunology; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000821:virology; D007378:Interleukins / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008253:Macaca mulatta; D012367:RNA, Viral / Q000097:blood / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D000098546:Interleukin-21
chemical_list: D044966:Anti-Retroviral Agents; D004279:DNA, Viral; D007378:Interleukins; D012367:RNA, Viral; D000098546:Interleukin-21