Interleukin-21 combined with ART reduces inflammation and viral reservoir in SIV-infected macaques

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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 ARTtreated, 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.

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  • Medicine(all)

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Micci, L., Ryan, E. S., Fromentin, R., Bosinger, S. E., Harper, J. L., He, T., ... Paiardini, M. (2015). Interleukin-21 combined with ART reduces inflammation and viral reservoir in SIV-infected macaques. Journal of Clinical Investigation, 125(12), 4497-4513. https://doi.org/10.1172/JCI81400