A Phase III Study of Recombinant Human Interferon Gamma to Prevent Opportunistic Infections in Advanced HIV Disease

Abstract

The efficacy and safety of recombinant human interferon gamma (rIFN-gamma) in the reduction of opportunistic disease in patients with advanced HIV-1 infection are assessed. A 12-month double-blind, placebo-controlled, multicenter, 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 received rIFN-gamma 0.05 mg/m(2) or 0.9% saline subcutaneously three times weekly 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 dispersion factor raised the p value to 0.13. rIFN-gamma appeared to have a particular effect on the incidence of Candida, herpes simplex, and cytomegalovirus infections. Three-year survival in the rIFN-gamma arm was 28% compared to 18% in the placebo group (not significant). rIFN-gamma-associated side-effects of headache, fatigue, rigors, influenza-like symptoms, depression, myalgia, and granulocytopenia were reversible. There was no evidence for HIV activation. Although not significant, the trend towards decreased opportunistic infections and increased survival warrants consideration of further trials of rIFN-gamma. The study gives additional information on the safety profile of this cytokine.

The Significance of Interferon-γ in HIV-1 Pathogenesis, Therapy, and Prophylaxis

“…In one study in South Africa, tuberculosis (TB) incidence rates during 8 years of follow-up showed substantially higher rates in HIV + subjects on long-term ART than in HIV uninfected individuals living in the same community (92). IFNγ has been used as adjunctive immunotherapy with or without ART for the treatment of HIV-associated opportunistic infections such as cryptococcal meningitis (61–63), Pneumocystis carinii (64, 65), Toxoplasma gondii (65), Candida albicans (64, 65), Mycobacterium avium (65, 66), and visceral leishmaniasis (65, 67). In a majority of the cases, adjunctive IFNγ therapy with or without other cytokines did not adversely affect the ART therapy for those on ART (i.e., maintained low to undetectable virus load) and did not increase CD4 + T cell counts in most HIV + patients except for those ART (61–66).…”

The Aryl Hydrocarbon Receptor Governs Epithelial Cell Invasion during Oropharyngeal Candidiasis

“…When administered prophylactically to patients with advanced HIV infection, IFN-γ appears to reduce the frequency of OPC (25). The salutary effects of IFN-γ on the host’s defense against C. albicans infection have been thought to be due to enhanced antigen presentation and phagocyte activity (26).…”

Interferon-gamma as adjunctive immunotherapy for invasive fungal infections: a case series

“…As such, it has been implicated as a treatment option in (invasive) fungal infections [20,21]. Moreover, limited evidence suggests that recombinant IFN-γ (rIFN-γ) has a beneficial effect on the outcome of fungal infections in patients with chronic granulomatous disease (CGD) [22], HIV [23-25], leukemia [26,27], and in patients receiving organ transplants [28]. However, it has not been investigated whether rIFN-γ actually enhances the immune response in these patients to explain these beneficial clinical effects.…”