UNC Receives NIH Grant to Develop and Test New Drugs to Block HIV Infection

Scientists at the University of North Carolina at Chapel Hill schools of medicine and pharmacy have been awarded a $3 million federal grant to develop and test a new generation of treatments aimed at preventing sexual transmission of HIV to uninfected individuals. This remains the most common cause of HIV infection worldwide.

The new NIAID award is titled "Next Generation Pre-Exposure Prophylaxis," or PrEP. "This project combines the strengths of four outstanding investigators with highly complementary skills, at UNC and our industrial partner, Merck," says J. Victor Garcia-Martinez, PhD, the projects principal investigator and professor of medicine, and a member of UNCs Center for Infectious Diseases and Center for AIDS Research.

Project collaborators with Garcia-Martinez are Angela Kashuba, PharmD, associate professor, and Russell Mumper, PhD, McNeill Distinguished Professor, both in the UNC Eshelman School of Pharmacy, and Daria Hazuda, PhD, at Merck Research Laboratories. Merck will not receive federal funding from this award. "We will address issues of fundamental importance to the next generation of PrEP agents," Garcia-Martinez said.

The new grant from the National Institute of Allergy and Infectious Diseases (NIAID) follows the July 11 announcement of a $32 million award from the agency to UNC to lead scientists from eight other universities in the search for ways to purge hidden HIV from the immune systems of infected patients taking antiretroviral therapy.

"This new award serves as further testament to the outstanding environment for conducting state-of-the-art AIDS research at UNC and will strengthen the close ties between our programs in medicine and pharmacy," Garcia-Martinez adds.

According to Garcia-Martinez, significant progress has been made in developing measures to prevent HIV infection, but recent results of clinical trials reveal that "the level of protection observed is suboptimal and that there is significant room for further improvement."

The UNC scientist also points out that most of the trials that are ongoing now involve drugs that are used for treatment, and to which there is drug-resistance in many parts of the world. "If you use for prevention the same drug you use for treatment, you may encounter situations where drug-resistant viruses might emerge. So we need to be ahead of the virus and to start working on HIV therapies that will be available for the next generation, which is the aim of this NIH initiative."

The new project will explore candidate drugs, experimental compounds, not yet tested in people. Preclinical experiments will be conducted in humanized BLT mice.

The "BLT" name is derived from the fact that these designer mice are created one at a time by introducing human bone marrow, liver and thymus tissues into animals without an immune system of their own.

Humanized BLT mice have a fully functioning human immune system and can be infected with HIV in the same manner as humans. The laboratory of Garcia-Martinez has pioneered the development of this humanized mouse model. "Prevention of sexual transmission of HIV is urgently needed," he says.