Trial Information

A Phase IV Randomized Study of the Use of Fluconazole as Chronic Suppressive Therapy Versus Episodic Therapy in HIV Positive Subjects With Recurrent Oropharyngeal Candidiasis

This study will evaluate two different management strategies for patients with advanced HIV
infection who are at risk for recurrent and fluconazole-refractory oropharyngeal
candidiasis. The treatment duration will be at least 24 months in order to evaluate the
long-term effects of the treatment strategies on the development of fluconazole-refractory
thrush. In addition to investigating antifungal treatment as it relates to
fluconazole-refractory infections, the study will evaluate host factors and organism-related
factors in order to increase our understanding of the pathogenesis of oropharyngeal
candidiasis and fluconazole-refractory infections.

Prior to randomization to a long-term management strategy using fluconazole, patients are
stratified into one of three groups according to their baseline CD4+ count (cells/mm3):
0-49, 50-100, and 101-150. Patients without oropharyngeal candidiasis (no thrush present) at
enrollment and those patients who respond (no thrush present) to the initial acute therapy
for an active infection are randomized 1:1 to one of two management strategies for
fluconazole: Arm A (episodic therapy) or Arm B (chronic suppressive therapy with continuous
fluconazole). Patients are then followed for a duration of 24 months after enrollment of
the last subject. Patients with active oropharyngeal candidiasis at time of enrollment will
be treated with fluconazole for up to 2 weeks and patients who respond (no thrush present)
are then randomized to a long-term management strategy. Those who do not respond (refractory
disease) to the acute treatment are permanently discontinued from the study. Women in both
groups will have the option of being treated for vulvovaginal candidiasis either through or
outside the study.