Interferons and interferon (IFN)-inducible protein 10 during highly activeanti-retroviral therapy (HAART) - possible immunosuppressive role of IFN-alpha in HIV infection

Interferons play an important, but incompletely understood role in HIV-rela ted disease. We investigated the effect of HAART on plasma levels of IFN-al pha, IFN-gamma, 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-alpha compared with healt hy controls (n = 19), with particularly high levels in advanced disease. HA ART induced a marked decrease in levels of both IFN-alpha, neopterin and IP -10, though not to normal concentrations. In contrast, IFN-gamma levels wer e low throughout the study, and not different from controls. While neopteri n and IP-10 remained significantly decreased compared with baseline levels throughout the study, IFN-alpha levels returned to baseline at the end of t he study. Persistently high IP-10 and IFN-alpha levels were associated with immunological treatment failure and even high baseline levels of IFN-alpha appeared to predict immunological relapse. Furthermore, we found a markedl y suppressive effect of exogenously added IFN-alpha on phytohaemagglutinin- stimulated lymphocyte proliferation in both patients and controls, and this suppressive effect seemed not to involve enhanced lymphocyte apoptosis. Ou r findings suggest a pathogenic role of IFN-alpha in HIV infection, which m ay be a potential target for immunomodulating therapy in combination with H AART.