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Sharon L. Hillier

UPMC Media Relations 

Grant Funds Research to Develop Microbicide Barrier to HIV

PITTSBURGH, January 9, 2003 The National Institutes of Health (NIH) has awarded a grant of nearly $8 million to the University of Pittsburgh and Magee-Womens Research Institute (MWRI) to fund research aimed at developing a microbicide barrier to the human immunodeficiency virus (HIV), the virus that causes AIDS.

The grant, through the NIHs National Institute of Allergy and Infectious Diseases, marks the largest ever received thus far by project principal investigator Sharon Hillier, Ph.D., professor of obstetrics, gynecology and reproductive sciences and molecular genetics and biochemistry at the University of Pittsburgh School of Medicine .

I believe fervently in trying to find a way to help women protect themselves against sexually transmitted infections, including HIV, said Dr. Hillier, who is also a senior investigator at MWRI. Currently, women have no way to protect themselves except condoms, and women do not control condom use.

Dr. Hillier and her colleagues will pursue several scientific projects that involve UC781, a tight-binding molecule discovered by co-principal investigator Michael Parniak, Ph.D., professor of medicine in the division of infectious diseases at the University of Pittsburgh School of Medicine. An organic molecule about the size of an antibiotic, UC781 is a non-nucleoside reverse transcriptase inhibitor that renders the HIV virus incapable of infecting cells.

These projects are:

Dr. Parniak will perform critical new studies evaluating the microbial activity of UC781, alone and in combination with other active components, against a variety of strains of HIV. This project is designed to focus on the extraordinary genetic diversity of HIV and the corresponding need to inactivate a wide spectrum of viral strains. These early tests will be done in vitro to determine both the efficacy of UC781 against HIV and its safety for use.

Phalguni Gupta, Ph.D., professor and assistant chairman of the division of infectious diseases and microbiology at Pitts Graduate School of Public Health, will coordinate a project to determine toxicity and efficacy of UC781 on HIV transmission rates in pre-clinical studies.

Lisa Rohan, Ph.D., assistant professor of pharmaceutical sciences in Pitts School of Pharmacy, and Charles Isaacs, Ph.D., New York Institute for Basic Research on Staten Island, will work on ways to formulate UC781 with other active agents to improve potency, effectiveness and ease of use.

Early clinical studies by Dr. Hillier and Harold Wiesenfeld, M.D., assistant professor of obstetrics, gynecology and reproductive sciences at Pitts School of Medicine are planned using a formulation developed by project partner Biosyn Inc. to evaluate the safety and systemic absorption of UC781.

Biosyn is looking at three or four different compounds, Dr. Hillier said of the Philadelphia-area pharmaceutical manufacturer that specializes in the development of drugs for infectious disease and reproductive health. "There is such a tremendous public health need for this kind of preventive strategy against HIV.

Since the federal government published the first report of five men having unexplained immune dysfunction in 1981, HIV and AIDS have devastated health and economic power across the globe. Worldwide, 20 million people have died and 42 million currently are estimated to be infected.

Successful development of a safe, effective way to prevent transmission of the HIV virus with a microbicide barrier could positively impact millions of people. So far, the only products evaluated in large trials for HIV prevention in this way have been formulations of the spermicide nonoxynol-9. These were ultimately deemed not to be protective against HIV.

In 1986, women made up 7 percent of new AIDS cases. Recent studies from the United Nations program on AIDS and the World Health Organization have found that about half the people now infected with AIDS worldwide are women. And more than 25 percent of new infections are among women. There are biological and cultural factors that put women at higher risk for acquiring HIV. Male-to-female virus transmission is more efficient than female-to-male.

In sub-Saharan Africa, a region already in crisis due to AIDS, 58 percent of infected adults are women.

Every 10 years, someone reports that there will be a vaccine against AIDS within the next 10 years, said Dr. Hillier. We hope to have an effective microbicide that can protect women against HIV in the next seven to eight years.

Both vaccine and microbicide HIV-prevention strategies are needed, she continued. Microbicide development has raised the bar for women's health products.

Other investigators involved in this effort are Marijane Krohn, Ph.D., associate professor of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine and an assistant investigator at MWRI; Bernard Moncla, Ph.D., research associate professor in the division of microbiology and biochemistry at Pitts School of Dental Medicine; and Dorothy Patton, Ph.D., professor of obstetrics and gynecology at the University of Washington in Seattle.

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