Oropharyngeal candidiasis is the most frequently occurring opportunistic infection in persons infected with human immunodeficiency virus (HIV). There tends to be high relapse rates with first-line therapies such as topical clotrimazole or nystatin, and systemic azole therapy (ketoconazole, fluconazole or itraconazole) is usually required. However, a marked increase has been seen in the number of fluconazole-resistant cases. Some small studies have found that itraconazole suspension is effective in patients with oral candidiasis. Phillips and colleagues performed a randomized double-blind study to compare the safety and efficacy of itraconazole oral solution with fluconazole capsules for the treatment of oropharyngeal candidiasis in patients with acquired immunodeficiency syndrome.
Patients enrolled in the study included HIV-infected adults who were at least 19 years old, had CD4 lymphocyte counts of less than 400 per mm3 (400 × 106 per L) and pseudomembranous oropharyngeal candidiasis documented by mycologic culture. Patients were excluded if they had taken any oral azole within the past two weeks, had esophageal involvement of disease, alanine or aspartate aminotransferase levels greater than five times the upper limit of normal or a creatinine clearance less than 50 mL per minute (0.84 mL per s). Patients were randomized to receive either fluconazole capsules (100 mg daily for 14 days) or itraconazole oral solution (either 100 mg daily for 14 days or 100 mg twice daily for seven days).
The patients were evaluated on the eighth and 15th days of treatment and again at one week and two weeks during follow-up. Clinical assessment was quantified with a scoring system that included the severity of signs and symptoms as well as the extent of the lesions. Responses were classified as complete, markedly improved, moderately improved, unchanged or deteriorated. Mycologic assessment was performed by microscopy (KOH, Gram stain or methylene blue stain) and culture. To assess safety and adverse events, hematologic and biochemical laboratory tests were performed 24 hours before enrollment, as well as on days 8 and 15 of treatment and at the end of the two-week follow-up period.
A total of 194 patients completed the trial. Baseline characteristics, including sex, mean age and average CD4 cell counts (approximately 150 per mm3 [150 × 106 per mL]), were essentially the same for all three groups. An acceptable clinical response viewed as complete or markedly improved was achieved in 90 percent of the patients receiving fluconazole; 90 percent of the patients receiving itraconazole once daily, and 82 percent of the patients receiving itraconazole twice daily. At day 14 of treatment, cultures were negative in 53 percent of the patients receiving fluconazole, 57 percent of the patients receiving itraconazole once daily and 44 percent of the patients receiving itraconazole twice daily. The clinical relapse rates within 18 days after treatment were 34 percent in the group receiving fluconazole, 35 percent in the group receiving itraconazole once daily and 37 percent in the group receiving itraconazole twice daily. There was no difference in adverse events among the three treatment groups. Gastrointestinal problems were the most commonly reported adverse events. There were no consistent changes in biochemical or hematologic parameters, although patients in each of the three groups had abnormalities at baseline. The frequency of abnormalities was considered to be reflective of the underlying disease.
The authors conclude that itraconazole oral solution at a dosage of 100 mg once daily for 14 days or 100 mg twice daily for seven days is an effective treatment for oropharyngeal candidiasis. The longer course of itraconazole treatment appears to be therapeutically equivalent to the fluconazole regimen of 100 mg once daily for 14 days.