Center for the Dissemination of Ultra-Long-Acting Antiretroviral Release Technology: DART Resource Program

ABSTRACT Human immunodeficiency virus (HIV) is one of the top areas of the National Institutes of Health- funded nonhuman primates (NHP) research. Within this context, antiretroviral (ARVs) used in research for HIV pre-exposure prophylaxis and treatment require frequent dosing regimens. ARVs are often administered through daily oral dosing or repeated injections, which are costly as well as burdensome on animals, veterinary staff and operational resources. Moreover, inconsistency in dosing regimen or dosages could be detrimental to research outcomes. Given this, we propose the dissemination of a drug-agnostic ultra-long-acting subcutaneous drug delivery implant, the NanoDDI, as a research tool for NHP studies, through the Center for the Dissemination of Ultra-Long-Acting Antiretroviral Release Technology: DART Resource Program. The DART Program will provide the NanoDDI for use in NHP studies on HIV for long- term ARV release to replace conventional modes of administration. Sustained and constant ARV delivery from the NanoDDI is achieved through controlled drug diffusion across a nanofluidic membrane without pumps or ports. The NanoDDI technology is immediately ready for use and rapid and reproducible manufacturing permits widespread facile dissemination. The drug-agnostic technology is supported by 10 years of development and deployment in various animal models, with demonstrations of long-term sustained release of various ARVs in NHP for up to 29 months without interruption. The central tenet of the HIV-related NHP studies and alleviate animal, operational and financial burden associated with conventional administ ation methods. The aims of the proposed DART Program, which will be pursued concurrently over five DART Program is that the NanoDDI can standardize ARV delivery across wide-ranging years, are, Aim 1: Outreach and Dissemination of NanoDDI for HIV Research in NHP, Aim 2: Integration and Deployment of NanoDDI for ARV Delivery in Independent Users’ Laboratories, and Aim 3: Broaden the Spectrum of Applicability of NanoDDI within the HIV Research Community. Outreach initiatives will create awareness and promote adoption of the NanoDDI into current and future NHP HIV research. The DART Program will ensure standardized NanoDDI deployment in Users’ NHP studies for reproducible research outcomes through comprehensive training, supported by our research and veterinary staff, and Veterinary Scientific Advisory board. Concurrently, User-generated data and User-introduced novel ARVs could enhance outreach as well as broaden NanoDDI drug portfolio. Altogether, research outcomes and dataset generated inclusive of ARV pharmacokinetic and User-specific data, could be used to fill knowledge gaps, improve drug delivery and accelerate drug development in HIV research. Expected outcomes of the DART Program include: successful integration of the NanoDDI into NHP HIV studies with significant cost and burden reduction, increase research output due to cost- and time-efficient changes in ARV delivery protocols, higher quality research data due to less variability in ARV delivery, and minimize scientific and financial risks associated with NHP research.