In a multicenter clinical trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), weekly doses of the drug fluconazole safely prevented certain common yeast infections and was not associated with adverse events or drug resistance. This is the first large, long-term study of HIV-infected women to evaluate whether fluconazole, which is used to treat yeast infections, can prevent them as well.

Paula Schuman, M.D., from Wayne State University, Detroit Medical Center, will present the research findings today at the XIth International Conference on AIDS in Vancouver, British Columbia.

"This study is part of NIAID's concentrated effort to develop better prevention and treatment strategies specifically targeted to HIV-infected women," says Steven Schnittman, M.D., assistant director for clinical research, NIAID Division of AIDS. "Fluconazole appears to safely and effectively prevent mucosal candidiasis, the most common fungal infection affecting women with HIV. In addition, the effectiveness of the drug is not at the expense of clinical resistance."

Vaginal yeast infections are common and easily treated in most women. They usually are caused by Candida albicans, a yeast that normally lives in the body. HIV-infected women, however, frequently develop yeast infections of the mouth, vagina and throat that are particularly persistent and difficult to treat, often increasing in severity as their immune systems weaken.

"The study proves that fluconazole has a useful role in the clinical management of HIV-infected women at risk for recurrent yeast infections," says Dr. Schuman. "As more and more women become infected with HIV and strategies of how best to use this class of drugs continue to be debated, this research provides some needed answers."

In the NIAID trial, called the Women's Fungal Study or CPCRA 010, 323 HIV-infected women with CD4+ T cell counts of less than 300 cells/mm³ of blood were randomly assigned to receive 200 mg of fluconazole once a week or placebo. After a median follow-up period of 29 months, fluconazole reduced the risk of at least one yeast infection of the mouth and vagina by 44 percent. The drug reduced the risk of oral candidiasis by 50 percent and vaginal candidiasis by 38 percent. During the study, 41 patients on fluconazole and 23 on placebo experienced at least one adverse event; however, no serious toxicities were seen. The researchers also looked at the effect of fluconazole on yeast infections of the throat and on invasive fungal disease, but too few cases occurred in each arm of the study to determine with statistical certainty if fluconazole prevented these conditions.

In a substudy, researchers investigated Candida resistance to fluconazole both clinically and in the test tube. Of those women who developed yeast infections, only 13, six in the fluconazole group and seven in the placebo group, developed clinical resistance to the drug after treatment. "This finding demonstrates that the resistance rates did not differ between the two groups, indicating that the regimen of fluconazole used was not associated with clinical resistance," says Dr. Schuman. "The in vitro resistance results currently are being analyzed."

The fluconazole study was conducted at 14 sites of the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA), one of three national AIDS clinical trials networks supported by NIAID.

NIAID, a component of the National Institutes of Health (NIH), conducts and supports research to prevent, diagnose and treat such illnesses as AIDS and other sexually transmitted diseases, tuberculosis, asthma and allergies. NIH is an agency of the U.S. Public Health Service, U.S. Department of Health and Human Services.