July 25, 2011
Angela Kashuba, PharmD, is concerned that the current approach to developing drug therapies to prevent HIV infection is backwards.
“We know that administering large doses of HIV drugs in animal models can prevent infection, but this information doesn’t directly help us prevent infections in people,” she says. “In this particular case, the doses being used in animals may be too toxic for people.”
“We need to make more informed progress toward protecting people, and it’s time we changed the paradigm.”
In support of this goal, the National Institute of Allergy and Infectious Diseases award a grant to the UNC Eshelman School of Pharmacy worth up to $2.17 million over three years. Kashuba is the principal investigator on the grant, titled “Preventing HIV Infection in Women: Targeting Antiretrovirals to Mucosal Tissues.” She is the director of the UNC Center for AIDS Research Clinical Pharmacology and Analytical Chemistry Core and an associate professor in the Division of Pharmacotherapy and Experimental Therapeutics.
Kashuba plans to determine exactly how much of a drug is needed to protect the mucosal surfaces through which HIV is typically contracted, and to build mathematical models that will predict optimal drug regimens and dosing strategies for HIV prevention. Kashuba has assembled a multidisciplinary team of clinicians and researchers to achieve this goal, including those specializing in infectious diseases, virology, pathology, gynecology, gastroenterology, pharmacometrics, analytical chemistry, regulatory environments, and clinical trial operations.
“This research adds to UNC’s HIV prevention and cure initiatives. It is aimed at using human tissues and safe doses of drugs to protect the uninfected instead of preventing those infected with the virus from transmitting it,” Kashuba says. “We are focused on optimizing the drug and the doses used, and are aiming for 100 percent efficacy using a safe dose.”
Ideally, Kashuba says she would like to maximize effectiveness while getting away from a daily dosing model, which has recently proven to be 40 to 60 percent effective in clinical studies.
“Ultimately, we want to be able to protect women who for many different reasons don’t want to advertise to their partners that they are concerned about HIV,” she says.
Kashuba has also received a $387,618 BRS Shared Instrumentation Grant from the NIH National Center for Research Services to equip her lab with a triple quadrapole mass spectrometer to support her group’s work. The machine is capable of precisely measuring extremely low concentrations of drug in very small samples of cellular material.
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