A Randomized Trial Comparing Fluconazole with Clotrimazole Troches for the Prevention of Fungal Infections in Patients with Advanced Human Immunodeficiency Virus Infection

William G. Powderly, Dianne M. Finkelstein, Judith Feinberg, Peter Frame, Weili He, Charles Van Der Horst, Susan L. Koletar, M. Elaine Eyster, John Carey, Hetty Waskin, Thomas M. Hooton, Newton Hyslop, Stephen A. Spector, Samuel A. Bozzette

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    Abstract

    Cryptococcal meningitis and other serious fungal infections are common complications in patients infected with the human immunodeficiency virus (HIV). Fluconazole is effective for long-term suppression of many fungal infections, but its effectiveness as primary prophylaxis had not been adequately evaluated. We conducted a prospective, randomized trial that compared fluconazole (200 mg per day) with clotrimazole troches (10 mg taken five times daily) in patients who were also participating in a randomized trial of primary prophylaxis for Pneumocystis carinii pneumonia. After a median follow-up of 35 months, invasive fungal infections had developed in 4.1 percent of the patients in the fluconazole group (9 of 217) and in 10.9 percent of those in the clotrimazole group (23 of 211; relative hazard, as adjusted for the CD4+ count, 3.3; 95 percent confidence interval, 1.5 to 7.6). Of the 32 invasive fungal infections, 17 were cryptococcosis (2 in the fluconazole group and 15 in the clotrimazole group; adjusted relative hazard, 8.5; 95 percent confidence interval, 1.9 to 37.6). The benefit of fluconazole was greater for the patients with 50 or fewer CD4+ cells per cubic millimeter than for the patients with higher counts. Fluconazole was also effective in preventing esophageal candidiasis (adjusted relative hazard, 5.8; 95 percent confidence interval, 1.7 to 20.0; P = 0.004) and confirmed and presumed oropharyngeal candidiasis (5.7 and 38.1 cases per 100 person-years of follow-up in the fluconazole and clotrimazole groups, respectively; P˂0.001). Survival was similar in the two groups. Fluconazole taken prophylactically reduces the frequency of cryptococcosis, esophageal candidiasis, and superficial fungal infections in HIV-infected patients, especially those with 50 or fewer CD4+ lymphocytes per cubic millimeter, but the drug does not reduce overall mortality.

    Original languageEnglish (US)
    Pages (from-to)700-705
    Number of pages6
    JournalNew England Journal of Medicine
    Volume332
    Issue number11
    DOIs
    StatePublished - Mar 16 1995

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    Clotrimazole
    Mycoses
    Fluconazole
    Virus Diseases
    HIV
    Candidiasis
    Cryptococcosis
    Confidence Intervals
    Cryptococcal Meningitis
    Pneumocystis Pneumonia
    CD4 Lymphocyte Count
    Lymphocytes
    Survival
    Mortality

    All Science Journal Classification (ASJC) codes

    • Medicine(all)

    Cite this

    Powderly, William G. ; Finkelstein, Dianne M. ; Feinberg, Judith ; Frame, Peter ; He, Weili ; Van Der Horst, Charles ; Koletar, Susan L. ; Eyster, M. Elaine ; Carey, John ; Waskin, Hetty ; Hooton, Thomas M. ; Hyslop, Newton ; Spector, Stephen A. ; Bozzette, Samuel A. / A Randomized Trial Comparing Fluconazole with Clotrimazole Troches for the Prevention of Fungal Infections in Patients with Advanced Human Immunodeficiency Virus Infection. In: New England Journal of Medicine. 1995 ; Vol. 332, No. 11. pp. 700-705.
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    abstract = "Cryptococcal meningitis and other serious fungal infections are common complications in patients infected with the human immunodeficiency virus (HIV). Fluconazole is effective for long-term suppression of many fungal infections, but its effectiveness as primary prophylaxis had not been adequately evaluated. We conducted a prospective, randomized trial that compared fluconazole (200 mg per day) with clotrimazole troches (10 mg taken five times daily) in patients who were also participating in a randomized trial of primary prophylaxis for Pneumocystis carinii pneumonia. After a median follow-up of 35 months, invasive fungal infections had developed in 4.1 percent of the patients in the fluconazole group (9 of 217) and in 10.9 percent of those in the clotrimazole group (23 of 211; relative hazard, as adjusted for the CD4+ count, 3.3; 95 percent confidence interval, 1.5 to 7.6). Of the 32 invasive fungal infections, 17 were cryptococcosis (2 in the fluconazole group and 15 in the clotrimazole group; adjusted relative hazard, 8.5; 95 percent confidence interval, 1.9 to 37.6). The benefit of fluconazole was greater for the patients with 50 or fewer CD4+ cells per cubic millimeter than for the patients with higher counts. Fluconazole was also effective in preventing esophageal candidiasis (adjusted relative hazard, 5.8; 95 percent confidence interval, 1.7 to 20.0; P = 0.004) and confirmed and presumed oropharyngeal candidiasis (5.7 and 38.1 cases per 100 person-years of follow-up in the fluconazole and clotrimazole groups, respectively; P˂0.001). Survival was similar in the two groups. Fluconazole taken prophylactically reduces the frequency of cryptococcosis, esophageal candidiasis, and superficial fungal infections in HIV-infected patients, especially those with 50 or fewer CD4+ lymphocytes per cubic millimeter, but the drug does not reduce overall mortality.",
    author = "Powderly, {William G.} and Finkelstein, {Dianne M.} and Judith Feinberg and Peter Frame and Weili He and {Van Der Horst}, Charles and Koletar, {Susan L.} and Eyster, {M. Elaine} and John Carey and Hetty Waskin and Hooton, {Thomas M.} and Newton Hyslop and Spector, {Stephen A.} and Bozzette, {Samuel A.}",
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    Powderly, WG, Finkelstein, DM, Feinberg, J, Frame, P, He, W, Van Der Horst, C, Koletar, SL, Eyster, ME, Carey, J, Waskin, H, Hooton, TM, Hyslop, N, Spector, SA & Bozzette, SA 1995, 'A Randomized Trial Comparing Fluconazole with Clotrimazole Troches for the Prevention of Fungal Infections in Patients with Advanced Human Immunodeficiency Virus Infection', New England Journal of Medicine, vol. 332, no. 11, pp. 700-705. https://doi.org/10.1056/NEJM199503163321102

    A Randomized Trial Comparing Fluconazole with Clotrimazole Troches for the Prevention of Fungal Infections in Patients with Advanced Human Immunodeficiency Virus Infection. / Powderly, William G.; Finkelstein, Dianne M.; Feinberg, Judith; Frame, Peter; He, Weili; Van Der Horst, Charles; Koletar, Susan L.; Eyster, M. Elaine; Carey, John; Waskin, Hetty; Hooton, Thomas M.; Hyslop, Newton; Spector, Stephen A.; Bozzette, Samuel A.

    In: New England Journal of Medicine, Vol. 332, No. 11, 16.03.1995, p. 700-705.

    Research output: Contribution to journalArticle

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    AU - Powderly, William G.

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    N2 - Cryptococcal meningitis and other serious fungal infections are common complications in patients infected with the human immunodeficiency virus (HIV). Fluconazole is effective for long-term suppression of many fungal infections, but its effectiveness as primary prophylaxis had not been adequately evaluated. We conducted a prospective, randomized trial that compared fluconazole (200 mg per day) with clotrimazole troches (10 mg taken five times daily) in patients who were also participating in a randomized trial of primary prophylaxis for Pneumocystis carinii pneumonia. After a median follow-up of 35 months, invasive fungal infections had developed in 4.1 percent of the patients in the fluconazole group (9 of 217) and in 10.9 percent of those in the clotrimazole group (23 of 211; relative hazard, as adjusted for the CD4+ count, 3.3; 95 percent confidence interval, 1.5 to 7.6). Of the 32 invasive fungal infections, 17 were cryptococcosis (2 in the fluconazole group and 15 in the clotrimazole group; adjusted relative hazard, 8.5; 95 percent confidence interval, 1.9 to 37.6). The benefit of fluconazole was greater for the patients with 50 or fewer CD4+ cells per cubic millimeter than for the patients with higher counts. Fluconazole was also effective in preventing esophageal candidiasis (adjusted relative hazard, 5.8; 95 percent confidence interval, 1.7 to 20.0; P = 0.004) and confirmed and presumed oropharyngeal candidiasis (5.7 and 38.1 cases per 100 person-years of follow-up in the fluconazole and clotrimazole groups, respectively; P˂0.001). Survival was similar in the two groups. Fluconazole taken prophylactically reduces the frequency of cryptococcosis, esophageal candidiasis, and superficial fungal infections in HIV-infected patients, especially those with 50 or fewer CD4+ lymphocytes per cubic millimeter, but the drug does not reduce overall mortality.

    AB - Cryptococcal meningitis and other serious fungal infections are common complications in patients infected with the human immunodeficiency virus (HIV). Fluconazole is effective for long-term suppression of many fungal infections, but its effectiveness as primary prophylaxis had not been adequately evaluated. We conducted a prospective, randomized trial that compared fluconazole (200 mg per day) with clotrimazole troches (10 mg taken five times daily) in patients who were also participating in a randomized trial of primary prophylaxis for Pneumocystis carinii pneumonia. After a median follow-up of 35 months, invasive fungal infections had developed in 4.1 percent of the patients in the fluconazole group (9 of 217) and in 10.9 percent of those in the clotrimazole group (23 of 211; relative hazard, as adjusted for the CD4+ count, 3.3; 95 percent confidence interval, 1.5 to 7.6). Of the 32 invasive fungal infections, 17 were cryptococcosis (2 in the fluconazole group and 15 in the clotrimazole group; adjusted relative hazard, 8.5; 95 percent confidence interval, 1.9 to 37.6). The benefit of fluconazole was greater for the patients with 50 or fewer CD4+ cells per cubic millimeter than for the patients with higher counts. Fluconazole was also effective in preventing esophageal candidiasis (adjusted relative hazard, 5.8; 95 percent confidence interval, 1.7 to 20.0; P = 0.004) and confirmed and presumed oropharyngeal candidiasis (5.7 and 38.1 cases per 100 person-years of follow-up in the fluconazole and clotrimazole groups, respectively; P˂0.001). Survival was similar in the two groups. Fluconazole taken prophylactically reduces the frequency of cryptococcosis, esophageal candidiasis, and superficial fungal infections in HIV-infected patients, especially those with 50 or fewer CD4+ lymphocytes per cubic millimeter, but the drug does not reduce overall mortality.

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