While the ability to investigate IFN-I signaling defects during latent infection of primary cells remains a challenge, we have recently demonstrated that the induction of various IFN-stimulated genes following IFN-α or polyinosinic:polycytidylic acid stimulation is impaired in cell lines latently infected with HIV-1 [9]. Here, IFNA1 is linked to disease arising from reactivation of latent virus.