Fluconazole vs. flucytosine in the treatment of esophageal candidiasis in AIDS patients: a double-blind, placebo-controlled study.

BACKGROUND AND STUDY AIMS

Contrasting opinions exist as to the pharmacological treatment of esophageal candidiasis in human immunodeficiency virus (HIV)-positive patients. The aim of this study has been to evaluate the role, therapeutic efficacy, and the cost-benefit ratio of two antifungal drugs, fluconazole and flucytosine, compared with a placebo, in the treatment of endoscopically-diagnosed esophageal candidiasis in patients with acquired immune deficiency syndrome (AIDS).

PATIENTS AND METHODS

The study included 60 HIV-positive patients (38 males and 22 females, mean age 27 +/- 2) with a first episode of esophageal candidiasis diagnosed by endoscopy (grades I-II of Kodsi's endoscopic classification, and grades I-IIa of Barbaro's clinical classification). No other opportunistic infection of the esophagus was detected. In a double-blind procedure, patients were randomized into three groups of 20 patients each, receiving either fluconazole (3 mg/kg/daily per os), flucytosine (100 mg/kg/daily per os) or placebo. After two weeks of treatment, the patients previously assigned to receive the placebo were double-blindly randomized to receive fluconazole (eight patients) or flucytosine (nine patients). In order to evaluate the efficacy of pharmacological therapy, clinical examination was performed at weeks 2 and 5, and then every week up to the end of follow-up (three months); endoscopic examination was performed at weeks 2 and 5, and at the end of follow-up.

RESULTS

At week 2, endoscopic cure (grade 0) was observed in 13 patients (65%) of the fluconazole group and in three patients (15%) in the flucytosine group (relative risk ratio: 0.23; 95% C.I.: 0.10-0.48; p < 0.05), and a partial endoscopic response (grade I) was observed in two patients (10%) in the placebo group. Complete clinical remission (grade 0) was observed in 16 patients (80%) in the fluconazole group and 12 patients (60%) in the flucytosine group (relative risk ratio: 0.75; 95% C.I.: 0.42-0.89; p = n.s.), while six patients (30%) in the placebo group presented partial clinical remission (grade I). At the end of follow-up, endoscopic cure was observed in 19 patients (70%) in the fluconazole group and in nine patients (33%) in the flucytosine group (relative risk ratio: 0.47; 95% C.I.: 0.19-0.65; p < 0.05). Complete clinical remission was observed in 21 patients (77.7%) in the fluconazole group and in 17 patients (63%) in the flucytosine group (relative risk ratio: 0.81; 95% C.I.: 0.53-0.92; p = n.s.). No noticeable side-effects were observed in the patients in either treatment group, without a statistically significant difference in comparison with the placebo.

CONCLUSIONS

The results of this study have demonstrated that both fluconazole and flucytosine are safe and well tolerated in the treatment of esophageal candidiasis in AIDS patients. Fluconazole showed greater therapeutic efficacy than flucytosine, with a difference that was statistically significant in terms of the rate of endoscopic cure.