A Randomized Study of the Use of Fluconazole in Continuous versus Episodic Therapy in Patients with Advanced HIV Infection and a History of Oropharyngeal Candidiasis: AIDS Clinical Trials Group Study 323/Mycoses Study Group Study 40

• Published in: Clinical infectious diseases Vol. 41; no. 10; pp. 1473 - 1480
• Main Authors: Goldman, Mitchell, Cloud, Gretchen A., Wade, Karen D., Reboli, Annette C., Fichtenbaum, Carl J., Hafner, Richard, Sobel, Jack D., Powderly, William G., Patterson, Thomas F., Wheat, Lawrence J., Stein, David K., Dismukes, William E., Filler, Scott G.
• Format: Journal Article
• Language: English
• Published: United States The University of Chicago Press 15.11.2005; University of Chicago Press; Oxford University Press
• Subjects: Acquired immune deficiency syndrome; Adult; Aged; AIDS; AIDS-Related Opportunistic Infections - drug therapy; AIDS-Related Opportunistic Infections - microbiology; Antifungal Agents - administration & dosage; Antifungal Agents - therapeutic use; Antiretrovirals; Candidiasis; Candidiasis, Oral - complications; Candidiasis, Oral - drug therapy; CD4 Lymphocyte Count; Clinical trials; Drug Administration Schedule; Drug therapy; Female; Fluconazole - administration & dosage; Fluconazole - therapeutic use; Fungal infections; HIV; HIV Infections - complications; HIV/AIDS; Human immunodeficiency virus; Humans; Infections; Infectious diseases; Male; Medicine; Middle Aged; Oropharynx - microbiology; Risk factors; Symptoms; T lymphocytes; University administration
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/497373

Background. In human immunodeficiency virus (HIV)–infected patients, fluconazole prophylaxis is associated with reductions in the rate of fungal infection. However, concerns exist with regard to the use of fluconazole prophylaxis and the risk of development of fluconazole treatment—refractory infections. Methods. We performed a randomized, open-label trial that compared oral fluconazole given continuously (200 mg 3 times weekly; the “continuous fluconazole arm”) with fluconazole that was provided only for episodes of orophayngeal candidiasis (OPC) or esophageal candidiasis (EC) (the “episodic fluconazole arm”) in HIV-infected persons with CD4+ T cell counts of <150 cells/mm3 and a history of OPC. The primary study end point was the time to development of fluconazole-refractory OPC or EC, which was defined as lack of response to 200 mg fluconazole given daily for 14 or 21 days, respectively. Results. A total of 413 subjects were randomized to receive continuous fluconazole, and 416 were randomized to receive episodic fluconazole. After 42 months, 17 subjects (4.1%) in the continuous fluconazole arm developed fluconazole-refractory OPC or EC infections, compared with 18 subjects (4.3%) in the episodic fluconazole arm, with no difference between treatment arms with regard to the time to development of a fluconazole-refractory infection within 24 months (P = .88, by log-rank test) or before the end of the study (P = .97, by the log-rank test). Continuous fluconazole therapy was associated with fewer cases of OPC or EC (0.29 vs. 1.08 episodes per patient-year; P < .0001) and fewer invasive fungal infections (15 vs. 28 episodes; P = .04, by χ2 test), but not with improved survival, compared with episodic fluconazole therapy. Conclusion. Continuous fluconazole therapy is not associated with significant risk of fluconazole-refractory OPC or EC, compared with episodic fluconazole therapy, in HIV-infected patients with access to active antiretroviral therapy.