IFN-α blockade during ART-treated SIV infection lowers tissue vDNA, rescues immune function, and improves overall health

Type I IFNs (TI-IFNs) drive immune effector functions during acute viral infections and regulate cell cycling and systemic metabolism. That said, chronic TI-IFN signaling in the context of HIV infection treated with antiretroviral therapy (ART) also facilitates viral persistence, in part by promoting immunosuppressive responses and CDR+ T cell exhaustion. To determine whether inhibition of IFN-alpha might provide benefit in the setting of chronic, ART-treated SIV infection of rhesus macaques, we administered an anti-IFN-alpha antibody followed by an analytical treatment interruption (ATI). IFN-alpha blockade was well-tolerated and associated with lower expression of TIIFN-inducible genes (including those that are antiviral) and reduced tissue viral DNA (vDNA). The reduction in vDNA was further accompanied by higher innate proinflammatory plasma cytokines, expression of monocyte activation genes, IL-12-induced effector CDR+ T cell genes, increased heme/metabolic activity, and lower plasma TGF-beta levels. Upon ATI, SIV-infected, ART-suppressed nonhuman primates treated with anti-IFN-alpha displayed lower levels of weight loss and improved erythroid function relative to untreated controls. Overall, these data demonstrated that IFN-alpha blockade during ART-treated SIV infection was safe and associated with the induction of immune/erythroid pathways that reduced viral persistence during ART while mitigating the weight loss and anemia that typically ensue after ART interruption.

Automated summary

The study demonstrates that inhibiting IFN-alpha in conjunction with antiretroviral therapy (ART) can reduce viral persistence, improve weight loss and anemia in SIV-infected monkeys.