A phase III study of recombinant human interferon gamma to prevent opportunistic infections in advanced HIV disease

The efficacy and safety of recombinant human interferon gamma (rIFN-gamma) in the reduction of opportunistic disease in patients with advanced HIV-1 i nfection are assessed. A 12-month double-blind, placebo-controlled, multice nter, Phase III trial of rIFN-gamma in HIV-positive patients with CD4 < 100 x 10(9)/liter on stable antiretroviral therapy. Eighty-four patients were allocated treatment on a 1: 1 basis to rIFN-<gamma> or placebo. Patients re ceived rIFN-gamma 0.05 mg/m(2) or 0.9% saline subcutaneously three times we ekly for 48 weeks (optional extension to 18 months). The primary end point was the incidence of opportunist infections (CDC categories B/C). Secondary end points included mortality, immunological, and virological parameters. Patients on placebo had a mean of 3.45 opportunist infections (OIs) in the first 48 weeks. Patients treated with rIFN-gamma had a mean of 1.71 OIs (p = 0.04). However, the model showed overdispersion and the inclusion of a di spersion factor raised the p value to 0.13. rIFN-gamma appeared to have a p articular effect on the incidence of Candida, herpes simplex, and cytomegal ovirus infections. Three-year survival in the rIFN-gamma arm was 28% compar ed to 18% in the placebo group (not significant). rIFN-gamma -associated si de-effects of headache, fatigue, rigors, influenza-like symptoms, depressio n, myalgia, and granulocytopenia were reversible. There was no evidence for HIV activation. Although not significant, the trend towards decreased oppo rtunistic infections and increased survival warrants consideration of furth er trials of rIFN-gamma. The study gives additional information on the safe ty profile of this cytokine.