Novel approaches are urgently needed to achieve the next level of control of HIV infection beyond antiretroviral medications that will lead to the ultimate goal of curing HIV infection. Exploiting the innate immune system control of HIV is one possible component of that strategy with pegylated interferon α representing a well-characterized agent that is being applied to this effort.In this review, the authors summarize the history of interferon α treatment in the setting of HIV infection with a focus on clinical trials that examined the downstream effects on innate immune responses. More recently, clinical trials that administered pegylated interferon α-2a have demonstrated which interferon-stimulated genes are associated with its antiviral effects and which of these host-restriction factors may play a role in limiting the magnitude of the HIV reservoir.The potential to exploit interferon α as part of a cure strategy is provocative. Whether key interferon-induced antiviral factors can be upregulated sufficiently to affect the reservoir is unknown. Additional research employing pegylated interferon α-2a is needed to identify which innate immune pathways are candidate targets for novel biological therapies for the potential cure of HIV infection.
