Cytotoxic CD4+ T-cells during HIV infection: Targets or weapons?

•Antigen-specific CD4+ CTLs are readily detectable in HIV-infected patients.•Type-I IFN and IL-2 are important signals for CD4+ CTLs differentiation.•CD4+ CTLs exhibit a late-differentiated memory phenotype during HIV infection.•CD4+ CTLs possess granule-dependent and independent effector mechanisms.•CD4+ CTLs cooperate with other cytotoxic cells for the lysis of infected cells.