Fluconazole as Prophylaxis Against Fungal Infection in Patients With Advanced HIV Infection

Abstract

There is limited information regarding the usefulness of primary antifungal prophylaxis in patients with advanced human immunodeficiency virus (HIV) disease. To evaluate the efficacy and safety of oral fluconazole treatment for the prevention of systemic fungal diseases related to the acquired immunodeficiency syndrome. We evaluated the clinical records of more than 1300 HIV-infected patients followed up for 6 years to identify subjects with a CD4+ lymphocyte count less than 0.20 x 10(9)/L (200/microL) and no prior systemic fungal disease. We compared 128 patients who received oral fluconazole (100 mg/d every third week) with 121 subjects who received no antifungal treatment. The occurrence of visceral mycoses or death was considered an end point. The frequency of esophageal candidiasis and extrapulmonary cryptococcosis and their related clinical and laboratory features, as well as overall patient survival, were assessed and compared between the 2 study groups. Subjects not treated with fluconazole experienced a significantly higher incidence of systemic mycoses than patients who received fluconazole: 28.4 vs 8.8 cases per 100 patient-years (P < .001). Fluconazole treatment was more effective in preventing esophageal candidiasis than cryptococcosis and was more effective in subjects with a CD4+ cell count less than 0.10 x 10(9)/L. Moreover, fungal complications occurred later and were associated with a significantly lower CD4+ cell count among treated vs untreated patients, while the duration of antiretroviral therapy did not play a significant role. Although mortality rates were similar in the 2 study groups, the fatal outcome of disease was less frequently caused by a fungal disease in subjects who underwent fluconazole prophylaxis. Fluconazole had a favorable tolerability profile. In our experience, primary fluconazole prophylaxis proved safe and effective in the prevention of systemic candidiasis and cryptococcosis in patients with advanced HIV disease but it did not improve overall survival. Prospective controlled trials are advisable to confirm efficacy, to find the drug of choice and its best dosage and schedule of administration, to identify patient subgroups showing the most favorable cost-benefit ratios, and to evaluate the effects on overall life expectancy and the risk of emergence and spread of antifungal drug resistance.