Low-dose IFN-alpha monotherapy in treatment-naive individuals with HIV-1 infection: Evidence of potent suppression of viral replication

To evaluate the safety and antiviral action of interferon-alpha (IFN-alpha) in HIV-1 infection, we undertook a proof of concept study in 27 treatment- naive patients. Eligible patients comprised two groups: the IFN-alphaT grou p (n = 17), which received 5 MIU IFN-alpha s.c. daily for 32 consecutive da ys, and the IFN-alpha NT group (n = 10), which did not receive IFN-alpha pr ior to highly active antiretroviral therapy (HAART), which was commenced on day 28 in both groups. IFN-alpha treatment was well tolerated in 14 of the 17 patients of the IFN-alphaT group who completed the study. The mean HIV RNA reduction in the IFN-alphaT group on day 14 was 1.1 log(10). Viral load suppression was inversely associated with baseline viral load (p = 0.031). Four weeks after initiation of HAART, IFN-alphaT and IFN-alpha NT group pa tients had 2.40 and 1.82 log,() HIV RNA reduction from baseline, respective ly (p < 0.001). There was no evidence of cross-resistance with existing ant iretrovirals in patients with HIV-RNA rebound after initial plasma viral lo ad decline <greater than or equal to>1 log(10) during IFN-alpha monotherapy . Thus, low daily IFN-alpha exhibits potent anti-HIV-1 activity in vivo wit hout serious adverse effects. These properties render IFN-alpha an attracti ve candidate for further assessment as a constituent of HAART.