Ultra-long-acting delivery for the prevention and treatment of HIV/AIDS - The applicant seeks this K99/R00 award to achieve research independence focused on the integration of precision biomaterials and antiretroviral (ARV) therapy to innovate the treatment of HIV/AIDS. To achieve this goal, the applicant will receive training in three critical areas: (1) design of long-acting injectables (LAIs) to achieve sustained delivery of a broad spectrum of ARVs, (2) preclinical evaluation of LAIs in humanized HIV mouse models, and (3) pharmacokinetic analysis and modeling. She will receive guidance and comprehensive training through a detailed training plan from a mentoring team of experts (Drs. Joshi, Barouch, and Karp) with an established track record of mentoring junior scientists to independence. Her research will identify biodegradable LAIs that can provide sustained delivery of both hydrophobic and hydrophilic ARVs for at least 6 months with minimal initial burst and rapidly achievable steady- state plasma levels. During the K99 phase, she will investigate how the physicochemical properties of her LAI and ARV hydrophilicity can play a role in encapsulated ARV release and establish sustained prophylactic efficacy against HIV in a humanized mouse model. She will also tailor the LAI formulations to deliver a broad spectrum of ARVs, enabling single injection combination ARV therapy (cART) in vitro. This research goal, combined with the training and mentorship she will receive, will prepare her for independence in the R00 phase. During the R00 phase, she will utilize findings from the K99 phases for preclinical validation of sustained cART efficacy using her LAI in humanized mice and PK analysis in non-human primates. Ultimately, this research aims to provide a strong scientific rationale for future clinical trials, paving the way for a more accessible and effective approach to global HIV prevention and treatment that promotes health equity. Her findings during the K99 and R00 phases of this proposal will have a paradigm-shifting impact by providing robust scientific justification for future clinical trials, paving the way for a more accessible and effective approach to global HIV prevention and treatment, and promoting health equity. The K99/R00 award will thus provide the applicant with a platform for an independent career using versatile ultra-long-acting drug delivery, the HIV animal model, and human PK modeling to mitigate the HIV/AIDS epidemic.
