Could U of U Drug Stop HIV?

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A University of Utah research team has created a drug that may well be the next breakthrough in both HIV treatment and prevention.

For the last decade a research team at the University of Utah School of Medicine has been developing PIE12-trimer. This drug falls into the classification of medicines known as a microbicide — a substance (usually a gel) intended to prevent viruses and bacteria from infecting a host’s tissue. After several successful tests on HIV-infected vaginal tissue in lab conditions, team leader Michael S. Kay said that PIE12-trimer could be used for vaginal protection against HIV infection, and even to treat existing infection.

“We believe that PIE12-trimer could provide a major new weapon in the arsenal against HIV/AIDS. Because of its ability to block the virus from infecting new cells, PIE12-trimer has the potential to work as a microbicide to prevent people from contracting HIV and as a treatment for HIV infected people,” explained Kay, an assistant professor of microbiology at the medical school.

In 2009, QSaltLake reported about research being conducted in another lab at the medical school to create soft polymer rings that could be filled with antiretroviral drugs or other microbicides and then inserted vaginally to block HIV transmission during sex. This lab, lead by Patrick Kiser, an associate bioengineering professor, is working closely with the PIE12-trimer team, said Kay.

“My group is focused on deciding the drugs that would end up in such a ring,” he said.

PIE12-trimer is a class of peptide drug that, unlike regular peptides, does not degrade when inserted into the body. It works by joining three peptides (the PIE12 in its name) to form what Kay describes as a “pocket” on the surface of the HIV virus. The pocket then prevents the virus from entering and infecting a cell.

Like Kiser’s group, Kay’s research team is particularly concerned with stopping the spread of HIV in Africa, which has been hit harder by the virus than any other continent. Currently, the World Health Organization estimates that two-thirds of the world’s 33 million HIV patients live there. In order to make sure that PIE12-trimer is effective in Africa, Kay said that his lab has tested it on tissue infected with all known major HIV strains, including those that most commonly occur on this continent. The microbicide has been successful, he said, in blocking all of them. These results, along with PIE12-trimer’s unique structure, suggest that the microbicide could be an answer to the virus’ capacity for developing drug-resistant strains.

Kay said the drug’s effectiveness against all major types of HIV could indicate that the PIE12-trimer could be not just an effective prevention method, but a treatment method, a fact which could also make it beneficial for people with HIV who live in developed nations, and those in particular who have multiple strains of the virus.

“What makes it so special is we think it will be very nontoxic compared to existing drugs,” he said.

Currently, Kay and his team are raising money to begin testing the drug on rats. If animal tests are successful, they hope that human clinical trials can begin within two to three years. If the drug ultimately proves to treat and prevent HIV, Kay said that PIE12-trimer’s peptide design could be used to create similar drugs to stop other viruses.

The study’s co-authors are Brett D. Welch, Ph.D. and U of U graduate student J. Nicholas Francis. Contributors include Debra M. Eckert, Ph.D., and graduate students Joseph Redman and Matthew Weinstock.

The lab’s research has been funded by the National Institutes of Health and the university’s Research Foundation.

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