Interferon-gamma treatment in azole-resistant oropharyngeal candidiasis

Although C. albicans is one of the infections that generally quickly improve and resolve following the immune response after HAART, in patients whose HIV progresses due to a failing salvage regimen Candida can become a life threatening condition and azole resistant infection is an increasing clinical problem. This anecdotal report from the Gartnavel General Hospital in Glasgow, presented evidence of the successful use of interferon-gamma to treat azole resistant oropharyngeal candidiasis and advanced HIV disease.

The 31 year old HIV positive patient presented with recurrent oropharyngeal Candida albicans infection which was known to be clinically and microbiologically resistant to azole therapy (fluconazole MIC > 128 mg/l and itraconazole MIC > 16 mg/l). Previous episodes of C. albicans infection since his HIV diagnosis in 1992 had been treated successfully with courses of fluconazole, itraconazole and ketoconazole.

His CD4 count was 7 cells/mm3 (1%) and viral load was 48,000 copies/ml. He was highly antiretroviral experienced and at time of presentation was taking abacavir, 3TC and d4T. The patient refused therapy with intravenous amphotericin and therefore, interferon-gamma (1 mg sub-cutaneously three times weekly) was used to attempt to stimulate macrophage function (topical amphotericin and nystatin treatment was continued). Within 3 weeks of commencing this therapy there was a dramatic improvement in symptoms and signs of oropharyngeal candidiasis.

After 4 months interferon-gamma was discontinued and within 4 days there was recurrence of his symptoms. Interferon-gamma treatment was therefore re-introduced successfully.

The mechanism for the antimicrobial effect of IFN-g suggested in this study included macrophage activation, stimulation of antigen presentation, regulation of leucocyte – endothelium interaction and effects on cell proliferation and apoptosis. IFN-g increases the production of reactive oxygen radicals which then increases the candidiacidal activity of granulocytes.

Bodasing N, Seaton RA et al – Interferon-gamma in resistant oropharyngeal candidiasis in an HIV positive patient. Poster 383. 5th Intl Congress on Drug Therapy in HIV Infection, Glasgow. 22-26 October 2000.