Weekly fluconazole for the prevention of mucosal candidiasis in women with HIV infection. A randomized, double-blind, placebo-controlled trial. Terry Beirn Community Programs for Clinical Research on AIDS.

BACKGROUND: Candidiasis is a frequent complication of infection with the human immunodeficiency virus (HIV); however, few data exist about the natural history, prevention, and treatment of mucosal candidiasis in women.

OBJECTIVE: To evaluate the safety and effectiveness of weekly fluconazole prophylaxis for mucosal candidiasis in women infected with HIV.

DESIGN: Randomized, double-blind, placebo-controlled trial.

SETTING: 14 sites participating in the Community Programs for Clinical Research on AIDS (CPCRA).

PATIENTS: 323 women with HIV infection and CD4+ cell counts of 300 cells/mm3 or less.

INTERVENTION: 200 mg of fluconazole per week or placebo. Open-label fluconazole for candidiasis prophylaxis was permitted after two oropharyngeal or vaginal episodes or one esophageal episode.

MEASUREMENTS: Development of mucosal candidiasis, clinical and in vitro resistance of Candida species to fluconazole, survival, and adverse events.

RESULTS: After a median follow-up of 29 months, 72 of 162 patients receiving fluconazole and 93 of 161 patients receiving placebo had at least one episode of candidiasis (relative risk [RR], 0.56 [95% Cl, 0.41 to 0.77); P < 0.001). Weekly fluconazole was effective in preventing oropharyngeal candidiasis (RR, 0.50 [Cl, 0.33 to 0.74]; P < 0.001) and vaginal candidiasis (RR, 0.64 [Cl, 0.40 to 1.00]; P = 0.05) but not esophageal candidiasis (RR, 0.91 [Cl, 0.48 to 1.72]; P > 0.2). Relative risks were similar for women who had a history of mucosal candidiasis (RR, 0.5 [Cl, 0.35 to 0.75]) and those who did not (RR, 0.69 [Cl, 0.35 to 1.34]). Absolute risk reduction for patients with a history of infection was 25.6 per 100 person-years, which is more than twice the reduction of 11.2 per 100 person-years seen in patients with no history of infection. This difference reflects the higher risk of patients who previously had an infection. Candida albicans was not usually resistant to fluconazole in vaginal specimens in clinical or in vitro settings; such resistance occurred in less than 5% of patients in each group.

CONCLUSIONS: Weekly fluconazole (200 mg) seems to be safe and effective in preventing oropharyngeal and vaginal candidiasis. This regimen has a useful role in the management of HIV-infected women who are at risk for recurrent mucosal candidiasis.