Fluconazole Delays Fungal Infections In AIDS Patients
The drug fluconazole significantly delays the onset of fungal infections in people with AIDS according to a study supported by the National Institute of Allergy and Infectious Diseases (NIAID).
William Powderly, M.D., of the Washington University School of Medicine in St. Louis, Mo., plans to present the data at the First National Conference on Human Retroviruses and Related Infections in Washington, D.C., on Dec. 15.
The study, AIDS Clinical Trials Group (ACTG) 981, compared fluconazole to clotrimazole among HIV-infected patients who had fewer than 200 CD4+ T cells, the crucial immune system cell targeted by HIV.
Fungal infections, such as cryptococcal meningitis or candidiasis, are among the many opportunistic infections to which HIV-infected people become susceptible as their immune systems deteriorate. Up to 13 percent of AIDS patients develop cryptococcal infections, caused by a yeast-like fungus found in contaminated soil. The yeast Candida albicans is found naturally in most people and is the most common fungus to cause infections in patients with AIDS.
Begun in September 1989, the trial compared a single, 200 milligram (mg) daily tablet of fluconazole to five, 10 mg daily doses of clotrimazole lozenges in 428 participants randomly assigned to either therapy. The study closed to accrual in September 1992 and investigators followed patients through June 30, 1993.
According to the study investigators, the estimated two- year rate of invasive fungal infections, which are life- threatening, was 2.8 percent among patients assigned to fluconazole and 9.1 percent of those assigned to clotrimazole. In the study, 32 patients developed invasive fungal infections. Specifically, 17 patients developed cryptococcal infections: two of these patients received fluconazole and 15 took clotrimazole. When the scientist took into account the effect of the patients' initial CD4+ T cell counts, they found that patients randomized to clotrimazole had 3.25 times the risk of developing an invasive fungal infection when compared to patients taking fluconazole.
Fluconazole also provided a significant benefit in delaying superficial fungal infections of the mouth and skin. Among the participants, 46 developed such infections, including 10 patients taking fluconazole and 36 receiving clotrimazole. Presumed cases of superficial fungal infection occurred in another 83 patients, of whom 23 took fluconazole and 64, clotrimazole.
However, the overall benefit of widespread fluconazole use must be subject to future studies, Dr. Powderly notes, particularly because severe fungal infections among patients taking either fluconazole or clotrimazole were uncommon and the investigators found no evidence that fluconazole extended life.
All of the patients in this trial also participated in ACTG 081, which compared the ability of three different drug regimens combining zidovudine (AZT) with other drugs to prevent Pneumocystis carinii pneumonia, toxoplasmosis and serious bacterial infections. Patients in that trial randomly received 500 mg of AZT daily combined with trimethoprim/sulfamethoxazole (Bactrim) twice a day, 500 mg of AZT daily with 300 mg of aerosolized pentamidine (AP) every four weeks or 500 mg of AZT daily with 50 mg of dapsone twice a day.
For ACTG 981, Samuel Bozzette, M.D., of the University of California at San Diego, and Dr. Powderly served as protocol cochairs. Richard Hafner, M.D., of NIAID's Division of AIDS, served as medical officer.
NIAID, a component of the National Institutes of Health, supports research on AIDS, tuberculosis, allergies and other infectious diseases as well as immunology. NIH is an agency of the U.S. Public Health Service, U.S. Department of Health and Human Services.