Quantitative Pharmacology for Accelerating Drug Development for HIV/HCV Co-Infected Patients

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 DESCRIPTION (provided by applicant): This is an application for a K23 Mentored Patient-Oriented Career Development Award for Dr. Charles Venuto, PharmD, an assistant professor at the University of Rochester Medical Center. Dr. Venuto has established a strong foundation in clinical research with an emphasis in clinical pharmacology of HIV antiretrovirals and clinical tril methodologies. These training experiences have led to a focused and clear career path towards establishing himself as an independent investigator in HIV antiretroviral and hepatitis C virus (HCV) antiviral clinical pharmacology. Liver disease caused by HCV has now become a leading cause of serious illness and death in people with HIV; however, treatment advances in novel HCV therapies are just beginning to take shape in co-infected individuals. Although these new direct acting antivirals bring promising treatment strategies to the co-infected population, there are challenges that must be addressed in order to establish their safety and effectiveness. Drug-drug interactions, overlapping drug toxicities, increased pill burden, and pharmacokinetic (PK) variability have made it difficult to translate clinical study conclusions from mono-infected to co infected patient populations. With this in mind, Dr. Venuto's interests are focused in studying the pharmacokinetic and pharmacodynamic (PK/PD) patterns of drugs in patients with HIV and HIV/HCV, and identifying how these patterns influence clinical outcomes. The training and research plans within this K23 award have been devised around the hypothesis that alternative in silico tools such as model- based pharmacokinetic and drug-drug interaction studies, and data-driven approaches using preclinical and clinical trial data can be used to predict drug exposure, interaction potential and antiviral effects within HIV mono-infected and HIV/HCV co-infected individuals. This K23 award will serve as a vehicle for investigating this hypothesis by taking advantage of existing infrastructure within the NIH-sponsored AIDS Clinical Trials Group Network. Additionally, new pilot data will also be collected to compare antiretroviral PK between HIV mono- and co-infected patients, and to validate modeling tools developed from the clinical trial data. Dynamic research environments and a mentoring team comprised of leaders in clinical trial methodologies, HIV clinical pharmacology, and PK/PD modeling and simulation will facilitate the achievement of each goal. In conclusion, the model-based clinical pharmacology approaches proposed offer comprehensive and efficient ways to learn more about emerging treatment strategies for HIV/HCV patients.