Objective and design:Interferon α (IFNα), which is known to directly inhibit the HIV-1 replicative cycle and to increase the activity of cytotoxic T lymphocytes (CTL), is being tested as an anti-HIV agent. As CTL play a major role in immune defence against HIV, we wanted to further characterize CTL activity and the effect of IFNα on it.Methods:We followed by flow cytometry the intracellular expression of the key mediator of cytotoxicity, perforin, in peripheral blood T cells of patients treated with IFNα.Results:We observed that the percentage of T cells harbouring perforin was higher in infected subjects than in non-infected controls. Administration of IFNα2b attached to polyethylene glycol increased this perforin expression further and reduced viral load (P= 0.010). The increase in the percentage of T cells expressing perforin correlated with IFNα-induced decrease in viral load (r, 0.753;P= 0.003). In addition, the level of perforin expression before IFNα administration was inversely correlated with viral load remaining after IFNα administration (r, −0.647;P= 0.017).Conclusion:The pre-therapeutic percentage of perforin-positive T cells might be a predictive marker of the virological response to IFNα in HIV-1-infected patients.