The Targeted, Long-acting and Combination Anti-Retroviral Therapeutic (TLC-ART) Program has developed a scalable, drug-combination nano-platform technology called DcNPs (drug combination nanoparticles) that enables the stabilizing of insoluble and soluble short-acting antiretroviral drugs together in an injectable suspension. In nonhuman primates, DcNP is able to transform short-acting oral HIV-drug combinations into long-acting combinations that can be detected in plasma and cells with no lag phase (i.e., rapid peak drug concentrations). This application plans to leverage the novel DcNP technology to develop a safe and effective long-acting combination antiretroviral therapy for children with HIV. A long-acting injectable is urgently needed for children who struggle with adherence issues, including pill fatigue or an inability to swallow. We have established a public-private partnership for the most advanced two active drug TLC-ART platform evaluation intended for adult treatment through UM1 funding from the NIH. With these invaluable resources, we plan to create a long-acting monthly injectable formulation for children that includes three active drugs targeted to two HIV proteins. Our set of milestone-driven aims is based on a defined target product profile (TPP), and will be guided by an external advisory board (EAB) through scheduled and on-demand meetings. The research-focused objectives (Aims 1 and 2) are intended to evaluate a set of four different potential pediatric HIV-drug DcNP combinations and to select a candidate based on studies in juvenile non-human primates to progress to pre-clinical development and seek FDA guidance for an accelerated clinical progression plan (Aims 3-6). The five-year proposal will have EAB and NIAID/DAIDS program oversight to ensure success, and the study results will form a basis to develop safe and effective long-acting antiviral combinations for treatment of young children with HIV.
Lay abstract Following the 2018 U.S. Food and Drug Administration guidance on developing pediatric HIV drug products for global use, this application plans to accelerate research and development of a targeted drug-combination therapy in a long-acting injectable for children with HIV. A proven and innovative drug-combination nano-particle platform technology enables transformation of FDA-approved daily HIV drugs into a three-drug combination to be given monthly, which targets HIV host cells and tissues in the human body. This proposal plans to leverage pediatric user preference and contributions of industry partners to find a long-acting injectable that makes it easier for children with HIV to combat their disease, especially those with an inability to swallow or who have pill fatigue.
