This report will focus on new information on fungal infections presented at the 5th Conference on Retroviruses and Opportunistic Infections. As incidence rates for all types of HIV-related opportunistic infections have fallen there is less new information about the prevention and treatment of fungal infections, despite this there were several important reports at the conference.
Incidence Rates of Fungal Infections
The major focus of new information on opportunistic infections at the 5th conference was the continued decline in the rates of all types of opportunistic infections since the introduction of protease inhibitor containing combination therapy. The magnitude of the decline and more specific data on incidence rates among people receiving therapy were presented. One of the most comphrehensive sources of data on rates of all types of opportunistic infections was the French Clinical Epidemiologic Database (Costagliola Abst #182). In this ongoing prospective study, nearly 60,000 HIV infected adults are followed and data on clinical outcomes and CD4 counts are collected. Incidence rates for all types of infections were presented comparing the first half of 1996 to the first half of 1997. Rates of Esophageal candidiasis fell from 4.1 to 2.4 per 100 patient years (a decrease of 39%) and the rate of Cryptococcal disease fell from 0.7 to 0.2 per 100 patient years (a 68% decrease). Rates of mucosal candidiasis and histoplasmosis were not reported. No specific data on the use of fungal prophylaxis was reported from this cohort so it is not possible to determine how much of the decline was due to antiviral therapy alone.
COSTAGLIOLA, D. for the Clinical Epidemiology; Group from CISIH. INSERM SC4, Institut Saint-Antoine de Recherches en Sante, Paris, France. Abstract #182 Trends in Incidence of Clinical Manifestations of HIV Infection and Antiretroviral Prescriptions in French University Hospitals, 5th Conference on Retroviruses and Opportunistic Infections, Chicago, Feb 1-4, 1998.
Treatment for Refractory Oropharyngeal Candidiasis
Therapy for oropharnyngeal candidiasis in HIV infection includes the use of either topical therapy (clotrimazole or nystatin) or an oral azole (fluconazole or itraconazole). Generally when patients fail to respond to any of these therapies higher doses of fluconazole are used, but in some cases this is also unsuccessful. At this point the next treatment option is either a second azole or intravenous amphotercin. Intravenous amphotericin has the disadvantages if toxicity and the need for an intravenous lines, which usually requires hospitalization.
Vazquez and colleagues from Detroit reported on the use of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) as an adjuvant to fluconazole in refractory oropharyngeal candidiasis in patients with AIDS. GM-CSF is thought to increase the ability of white blood cells (neutrophils) to kill fungi. In this study three patients with advanced AIDS and CD4 counts < 10 who had severe oropharyngeal thrush that had not responded to high dose fluconazole (800 mg /d) or to amphotericin B were treated with daily GM-CSF 300ug/ subcutaneously and fluconazole 400 mg/d for 14 days. Prior to therapy all of the patients had cultures taken that showed the candida to be resistant to fluconazole (MIC > 80 ug/ml). All 3 of the patents had complete clinical resolution of their disease. Although this is a very small study the results suggest that GM-CSF may be a useful adjunct for treating fluconazole resistant thrush and this approach may prevent the need for amphotericin B. Due to the potential for GM-CSF to increase HIV replication it should be used in conjunction with antiretroviral therapy if possible.
J.A. VAZQUEZ, S. GUPTA, AND A. VILLANUEVA. Use of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) as an Adjuvant to Fluconazole in Antifungal Refractory Oropharyngeal Candidiasis in Advanced AIDS Patients. Abstract #491, 5th Conference on Retroviruses and Opportunistic Infections, Chicago, Feb 1-4, 1998.
Although we have seen dramatic reductions in the rates of opportunistic infections it is still unknown whether prophylaxis can be safely withdrawn in patients who have a sustained response to antiviral therapy. This question is under active investigation for a number of OI's. Gripshover and colleagues from Case Western withdrew suppressive fluconazole therapy in twenty patients with a history of mucosal candidiasis and who had responded to combination therapy including a protease inhibitor. The patients had been receiving azole therapy for an average of 18 months and had a range of CD4 counts (40-670) prior to the use of a PI. After PI therapy the median CD4 increase was 134 cells and 70% had an HIV RNA below the limit of detection. During an average follow-up of 5 months, two of the patients developed recurrent thrush at 30 and 90 days after stopping fluconazole. The authors reported that both patients who developed thrush had HIV RNA below the limit of detection and CD4 counts of 130 and 300, both responded to subsequent courses of fluconazole. The low rate of relapse and subsequent response to therapy in this study provide evidence that suppressive azole therapy may be able to be safely withdrawn. However, the finding that both patients who relapsed had sustained CD4 increases and continued HIV suppression provides evidence that the early immune recovery is incomplete. Further study of withdrawal of preventive therapy for fungal infections is warranted, both to define the outcome and to determine the best markers of patients who remain at risk despite increased CD4 cell numbers.
GRIPSHOVER BM, SALATA RA, VALDEZ H. LEDERMAN MM. Case Western Reserve University and University Hospitals of Cleveland, OH. Abstract # 489 Withdrawal of azole-suppressive therapy for thrush in patients responding to combination antiviral therapy including protease inhibitors. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, Feb 1-4, 1998.