Interferons and interferon (IFN)-inducible protein 10 during highly active anti-retroviral therapy (HAART)—possible immunosuppressive role of IFN-α in HIV infection

Interferons play an important, but incompletely understood role in HIV-related disease. We investigated the effect of HAART on plasma levels of IFN-α, IFN-γ, neopterin and interferon-inducible protein 10 (IP-10) in 41 HIV-infected patients during 78 weeks of therapy. At baseline HIV-infected patients had raised levels of both IP-10 and IFN-α compared with healthy controls (n = 19), with particularly high levels in advanced disease. HAART induced a marked decrease in levels of both IFN-α, neopterin and IP-10, though not to normal concentrations. In contrast, IFN-γ levels were low throughout the study, and not different from controls. While neopterin and IP-10 remained significantly decreased compared with baseline levels throughout the study, IFN-α levels returned to baseline at the end of the study. Persistently high IP-10 and IFN-α levels were associated with immunological treatment failure and even high baseline levels of IFN-α appeared to predict immunological relapse. Furthermore, we found a markedly suppressive effect of exogenously added IFN-α on phytohaemagglutinin-stimulated lymphocyte proliferation in both patients and controls, and this suppressive effect seemed not to involve enhanced lymphocyte apoptosis. Our findings suggest a pathogenic role of IFN-α in HIV infection, which may be a potential target for immunomodulating therapy in combination with HAART.