Type I IFN--a blunt spear in fighting HIV-1 infection.

•HIV-1 components can effectively trigger an innate immune response through various Pattern Recognition Receptors.•IFN is produced early during HIV-1 infection, but this initial response is dampened by viral escape mechanisms.•Immune clearance is prevented and the virus replicates and spreads, while establishing a persistent infection.•Prolonged and sustained stimulation of IFN during the chronic phase of infection drives chronic immune activation and inflammation.•Chronic immune activation and inflammation contribute to the immunopathogenesis of progressive HIV-1 disease.