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

L Micci, ES Ryan, R Fromentin… - The Journal of …, 2015 - Am Soc Clin Investig
L Micci, ES Ryan, R Fromentin, SE Bosinger, JL Harper, T He, S Paganini, KA Easley
The Journal of clinical investigation, 2015Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation