Fluconazole has been widely used to treat oropharyngeal candidiasis in patients with human immunodeficiency virus (HIV) infection. Resistance to fluconazole is becoming a serious problem, particularly with continuous low-dose use and multiple short courses of therapy. Revankar and colleagues conducted a prospective, randomized study to determine the frequency of oropharyngeal candidiasis and the development of resistance with intermittent or continuous use of fluconazole in patients infected with HIV.
HIV-infected patients with active oropharyngeal candidiasis were eligible for this study if their CD4 counts were less than 350 per mm3 (350 × 106 per L) and they were not currently taking any azole compound. Forty-four patients were randomized to receive continuous therapy or intermittent therapy with fluconazole. Patients were treated with 200 mg of fluconazole on day 1 and then with 100 mg per day for seven days or until complete resolution of the candidiasis. Patients assigned to the continuous treatment group continued to receive prophylaxis of 200 mg of fluconazole per day, whereas the patients assigned to the intermittent group received fluconazole only during a recurrence of candidiasis. Cultures were obtained every three months, and weekly during episodes of thrush. Resistance to fluconazole was evaluated in all of the culture samples. Other outcomes measured included occurrence of relapses and clinical failure.
All patients were followed for at least three months. The mean follow-up for the 16 patients who received continuous treatment was 11 months compared with 10.5 months in the 28 patients who received intermittent therapy. Symptomatic relapses occurred in 25 percent of patients receiving continuous therapy compared with 82 percent of patients receiving intermittent therapy. However, two thirds of the relapses that occurred in the continuous treatment group were associated with short breaks in the fluconazole regimen. Development of clinical resistance occurred in 13 percent of patients in the continuous group and 18 percent of patients in the intermittent group.
The authors also compared costs of the two regimens. The cost of continuous therapy was higher than that of intermittent therapy; however, for patients who had frequent relapses of candidiasis and needed higher dosages and longer courses of treatment, the cost of intermittent therapy approached that of continuous therapy.
The authors conclude that HIV-infected patients who have recurrent infections with oropharyngeal candidiasis may benefit from continuous suppressive therapy with fluconazole. They found no significant difference in the development of resistance, microbiologically or clinically, in either the intermittent or the continuous treatment groups. Further studies are needed to determine if patients at high risk for recurrences can be identified.