Julie B. Dumond, PharmD, BCPS, AAHIVE, Research Assistant Professor in the Division of Pharmacotherapy and Experimental Therapeutics at the UNC Eshelman School of Pharmacy, is a pharmacist with strong training and background in patient-oriented research methodology, and a proven commitment to applying these methods to improving antiretroviral (ARV) use in HIV-infected patients. The candidate's long-term-career goal is to be an independently funded, academic pharmacometrician, with a rich and diverse experience in pharmacokinetic/pharmacodynamic modeling of antiretroviral drugs. In particular, the candidate will pursue prospective population pharmacokinetic/pharmacodynamic (PK/PD) data collection, with the goal of quantifying age-related factors that influence drug response and toxicity. The candidate's short-term career goals fostered by this career development award are 1) to obtain formal training in advanced PK/PD, biostatistics, and computational methods, 2) to gain hands-on experience in population PK/PD modeling, 3) to foster working relationships with leading pharmacometricians, 4) to develop the preliminary data for an R34/U01 or R01 application, and 5) to expand her training in the responsible training of research. The proposed research plan, career development activities, and mentorship team are all uniquely suited to assist the applicant in achieving these goals. The research plan is built around the central hypothesis that: 1) altered ARV pharmacokinetics contributes to altered pharmacodynamics as measured by clinical response and toxicity, and 2) chronological age may only partly explain alterations in pharmacokinetics, and subsequently, pharmacodynamics. In this proposal, we will develop a pharmacokinetic and a pharmacokinetic/pharmacodynamic model in two specific aims for two common ARV regimens, emtricitabine/tenofovir/efavirenz (Atripla) and emtricitabine/tenofovir/atazanavir/ritonavir (Truvada, Reyataz, and Norvir). To accomplish these aims, we will use optimal sample design simulation to prospectively collect drug concentration and drug response data from HIV-infected adults receiving the regimens of interest. Subjects will be recruited from the University of North Carolina (UNC) Clinical HIV Cohort. To support the candidate's career development, she will pursue advanced coursework and independent study in the areas of pharmacokinetic and pharmacodynamic theory and modeling, biostatistics, computational methods, and research ethics, in concert with hands-on modeling training. The mentorship team, which includes internationally-recognized, independently-funded investigators with expertise in ARV clinical pharmacology (Kashuba), pharmacometrics (Forrest), and HIV clinical care and research (Cohen), will guide Dr. Dumond's research, training, and professional development. The research environment including the NIH-funded Translational and Clinical Sciences Institute and Center for AIDS Research at UNC and the Department of Pharmaceutical Sciences at the University at Buffalo, State University of New York, will provide a productive, collegial, and collaborative atmosphere in which to pursue the above research and training goals. NARRATIVE By 2015, more than 50% of the HIV-infected population in the United States will be at least 50 years of age, and little is known about the optimal clinical care of aging HIV-infected patients. The goal of this and subsequent research is to identify patient-specific factors modifying antiretroviral response and toxicity. This could lead to specific treatment recommendations for older HIV-infected patients.
By 2015, more than 50% of the HIV-infected population in the United States will be at least 50 years of age, and little is known about the optimal clinical care of aging HIV-infected patients. The goal of this and subsequent research is to identify patient-specific factors modifying antiretroviral response and toxicity. This could lead to specific treatment recommendations for older HIV-infected patients.
|Chen, Jingxian; Akhtari, Farida S; Wagner, Michael J et al. (2018) Pharmacogenetic Analysis of the Model-Based Pharmacokinetics of Five Anti-HIV Drugs: How Does This Influence the Effect of Aging? Clin Transl Sci 11:226-236|
|Dumond, J B; Collins, J W; Cottrell, M L et al. (2017) p16INK4a , a Senescence Marker, Influences Tenofovir/Emtricitabine Metabolite Disposition in HIV-Infected Subjects. CPT Pharmacometrics Syst Pharmacol 6:120-127|
|Collins, Jon W; Heyward Hull, J; Dumond, Julie B (2017) Comparison of tenofovir plasma and tissue exposure using a population pharmacokinetic model and bootstrap: a simulation study from observed data. J Pharmacokinet Pharmacodyn 44:631-640|
|Dumond, J B; Chen, J; Cottrell, M et al. (2017) Population Pharmacokinetics Modeling of Unbound Efavirenz, Atazanavir, and Ritonavir in HIV-Infected Subjects With Aging Biomarkers. CPT Pharmacometrics Syst Pharmacol 6:128-135|
|Chen, J; Malone, S; Prince, H M A et al. (2016) Model-Based Analysis of Unbound Lopinavir Pharmacokinetics in HIV-Infected Pregnant Women Supports Standard Dosing in the Third Trimester. CPT Pharmacometrics Syst Pharmacol 5:147-57|
|Dumond, Julie B; Francis, Owen; Cottrell, Mackenzie et al. (2016) Tenofovir/emtricitabine metabolites and endogenous nucleotide exposures are associated with p16(INK4a) expression in subjects on combination therapy. Antivir Ther 21:441-5|
|Maas, Brian M; Francis, Owen; Mollan, Katie R et al. (2016) Concentrations of Pro-Inflammatory Cytokines Are Not Associated with Senescence Marker p16INK4a or Predictive of Intracellular Emtricitabine/Tenofovir Metabolite and Endogenous Nucleotide Exposures in Adults with HIV Infection. PLoS One 11:e0168709|
|Dumond, Julie B; Rigdon, Joseph; Mollan, Katie et al. (2015) Brief Report: Significant Decreases in Both Total and Unbound Lopinavir and Amprenavir Exposures During Coadministration: ACTG Protocol A5143/A5147s Results. J Acquir Immune Defic Syndr 70:510-4|
|Dumond, Julie B; Yang, Kuo H; Kendrick, Racheal et al. (2015) Pharmacokinetic Modeling of Lamivudine and Zidovudine Triphosphates Predicts Differential Pharmacokinetics in Seminal Mononuclear Cells and Peripheral Blood Mononuclear Cells. Antimicrob Agents Chemother 59:6395-401|
|Adams, Jessica L; Patterson, Kristine B; Prince, Heather M A et al. (2013) Single and multiple dose pharmacokinetics of dolutegravir in the genital tract of HIV-negative women. Antivir Ther 18:1005-13|
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