Targeted Long-Acting Combination Antiretroviral Therapy (TLC-ART) Program

End Date: 
Jun 30 2020
Grant Source: 

NIH/NIAID UM1 AI120176; Rodney Ho, PI;  08/01/2015 – 07/31/20

Abstract:  (provided by applicant): Targeted Long-Acting Combination Antiretroviral Therapy (TLC-ART) The purpose of the University of Washington targeted long acting combination antiretroviral therapy program (UWTLC-ART) is to develop one or more safe, stable, scalable and tolerable long acting antiretroviral combinations for treatment of HIV infection in collaboration with NIH program staff. Leveraging the multidisciplinary, translational expertise and research infrastructure available at the University of Washington, this strategic drug development program integrates experts in statistics and mathematics, HIV adult and pediatric clinical trials, behavioral science, regulatory affairs, scientific and executive leadersip and business management, pharmaceutical sciences including drug targeting, delivery, metabolism and pharmacokinetics, retro virology, HIV primate models, preclinical pharmacology and toxicology, and mucosal immunology. The program has established collaborative relationships with major pharmaceutical industry and other stakeholders who can provide resources essential for the strategic development plan as well as potential future partnerships for product development. The program will also be guided by an external scientific advisory board (SAB) as well as an internal advisory group. We plan to develop three unique antiretroviral drug combination compositions/formulations, following a carefully monitored timeline. The drug combination choices are based on current antiretroviral combinations with demonstrated safety and efficacy. These drugs have known relationships between drug levels and therapeutic effect. The UWTLC-ART program utilizes a demonstrated capability to produce drug combination particles that achieve therapeutic plasma drug concentrations lasting more than seven days in a primate model. After subcutaneous injection, these compositions/formulations distribute widely throughout the lymphatic system. The program's strategic development decisions will be based on the target product profile, and will progress in accord with drug development timeline milestones. These decisions will guide prioritization of program resources to facilitate achieving the program goal. The program proposes developing three drug combinations, and will use progress on milestones, external information and the SAB to prioritize TLC-ART candidates advancing to the IND enabling studies and Phase 1 clinical trial. The program has 13 sections that are designed to interact in an integrated and collaborative way to achieve the program goal. To support the drug development, the program proposes three hypothesis-driven projects that will enhance our understanding of the distribution characteristics and safety using both pharmacokinetic/ pharmacodynamics modeling and in vivo studies. While the proposed Phase 1 clinical trial will study healthy adults, the compositions and drug development plan incorporate pediatric considerations with an eye toward future pediatric use. Although ambitious, the proposed program integrates experience and expertise, including those committed by major pharmaceutical companies to assure substantial progress in developing one or more targeted long acting antiretroviral treatments.