Abstract
Human immunodeficiency virus (HIV) infection induces chronic immune activation by stimulating both the innate and adaptive immune systems, resulting in persistent inflammation and immune cell exhaustion. Of note, the modulation of cytokine production and its release can significantly influence the immune response. Type I interferons (IFN-Is) are cytokines that play a crucial role in innate immunity due to their potent antiviral effects, regulation of IFN-stimulated genes essential for viral clearance, and the initiation of both innate and adaptive immune responses. Thus, an understanding of the dual role of IFN-I (protective versus harmful) during HIV-1 infections and elucidating its contributions to HIV pathogenesis is crucial for advancing HIV therapeutic interventions. This review therefore delves into the intricate involvement of IFN-I in both the acute and chronic phases of HIV infection and emphasizes its impact on viral persistence, immune activation, and immunometabolism in treated HIV-infected individuals.