March 24, 2006
Contact: Tom Capezzuto
Phone: (973) 972-3000
Researchers Find Antifungal Drug May Prevent Genital Transmission
-- Results bolster development of novel protections against HIV infection--
A drug that is globally available for treatment of genital yeast infections may also be effective in preventing the genital transmission of HIV. This discovery will be presented in a plenary lecture today (March 24) to the conference of the Society for Gynecologic Investigation in Toronto.
The study by a research team from the University of Medicine and Dentistry of New Jersey and the National Institutes of Health offers evidence that the drug, ciclopirox, totally blocks HIV from infecting freshly isolated human blood cells, and that it preferentially kills those cells that are infected by HIV.
The UMDNJ-NIH team said they are confident that the identification of the anti-HIV activity of ciclopirox will advance the entire field of microbicide development and practical use.
The researchers cautioned that their findings do not mean the currently available vaginal preparations of ciclopirox will protect against the genital transmission of HIV. Further studies must be conducted on the safety and efficacy of topical ciclopirox as a vaginal antiretroviral. Current ciclopirox preparations are safe only for the treatment of vaginal yeast infections, which rarely require administration for longer than two weeks. In fact, the researchers said, long-term self-administration of ciclopirox may actually damage the vaginal mucosa and degrade this natural barrier to HIV invasion, resulting in an increased probability of HIV infection by the genital route.
The concept for the study originated from discussions between Dr. Bernadette M. Cracchiolo, assistant professor and director of the Division of Gynecologic Oncology in the Department of Obstetrics, Gynecology and Women’s Health at UMDNJ-New Jersey Medical School and Dr. Hartmut M. Hanauske-Abel, assistant professor at UMDNJ-New Jersey Medical School and a scholar in the Department of Obstetrics, Gynecology and Women’s Health’s NIH BIRCWH (Building Interdisciplinary Research Careers in Women’s Health) Career Development Center, and an expert in the molecular processes needed for drug design.
They pointed out to their colleagues that ciclopirox, accepted worldwide for treatment of vaginal yeast infections, can block a key cellular protein that is recruited by HIV and therefore might also be effective in blocking the genital transmission of HIV.
This idea evolved into a research collaboration between investigators at UMDNJ-New Jersey Medical School and the National Institute for Dental and Craniofacial Research at NIH that has led to the findings presented at the conference. The senior collaborators from UMDNJ-New Jersey Medical School include Dr. Paul E. Palumbo, a physician renowned for his expertise in clinical trials of anti-HIV drugs; Dr. Michael B. Mathews, an internationally recognized expert in control of gene expression; and Dr. Tsafi Pe’ery, known for her work on nucleic acid formation by HIV. The senior collaborators from NIDCR-NIH are Dr. Myung H. Park and Dr. Edith C. Wolff.
The researchers knew that HIV relies on the protein-making machinery of the cells it infects and in particular recruits a protein termed ‘eukaryotic initiation factor 5A’, or eIF5A. In fact, the team published a landmark paper in 1998 that showed that the chemical blockade of eIF5A translates into a blockade of HIV infectivity. That paper presented experimental evidence for the team's theory that chemicals can inhibit the infectivity of HIV without directly targeting HIV or any of its components.
In pursuing this new research venture, the team decided that instead of developing such chemicals into novel drugs, they would use their expertise to examine the library of already existing drugs for potential inhibitors of eIF5A. Ciclopirox, a topical fungicide, was one of the existing drugs identified by the UMDNJ-NIH team as an antiretroviral pharmaceutical that does not target HIV directly.
The UMDNJ-NIH researchers found that at one one-thousandth (1/1000) of the concentration used in the standard vaginal preparation, ciclopirox blocked the fresh infection of cultured human blood cells by HIV isolated from patients. When administered to already infected cultures of human blood cells, ciclopirox not only decreased the number of viruses by a factor of at least 10,000, but also prevented the infection from returning for as long as 100 days after the end of treatment.
The researchers said further clinical studies of the anti-HIV activity of ciclopirox would have to rely on the expertise and the resources of the organizations that promoted the concept and pursued the preclinical and clinical testing of microbicides.