Acceptable Multi-user Biodegradable Extended Release (AMBER) Implant System for HIV Prevention

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PROJECT SUMMARY/ABSTRACT The overarching goal of this proposed program is to develop an innovative, end-user informed HIV pre- exposure prophylaxis (PrEP) product as an Acceptable Multi-user Biodegradable Extended Release (AMBER) implant. The implant technology addresses multiple challenges with current PrEP drug delivery systems (DDS) by offering beneficial attributes: user-independence and discretion of use, zero-order (sustained) release, long-term protection (≤1 year), retrievability and biodegradation of the polymeric implant. We propose to engineer the implant to be retrievable throughout the drug delivery period, in the case of adverse reactions or an end-user’s wish to discontinue. Otherwise, the AMBER implant will remain in-place and biodegrade after drug depletion. Uniquely, the AMBER implant decouples drug delivery features from biodegradation properties, which enables zero-order kinetics of drug release. The AMBER program addresses the goals of this National Institutes of Health (NIH) opportunity (RFA-AI-19-063) for the development of new and innovative sustained/extended release (SER) DDS for HIV PrEP with novel (non- tenofovir based) antivirals (ARV). We will inform implant development by eliciting preference insights from diverse gender, sexual orientation, and ethnic/racial minority populations in two priority geographical areas under “Ending the HIV Epidemic” initiative in the United States. We propose three specific aims: (1) develop the AMBER implant with polymers optimized for high durability and bioerosion profiles; (2) formulate selected ARVs and evaluate safety, pharmacokinetics, and efficacy of lead AMBER implants in preclinical studies; (3) identify Preferred User Characteristics (PUCs), inform technology development and future deployment of AMBER into practice by conducting iterative socio-behavioral research with Young MSM, cis- and trans- gender women in California and Alabama. We will strive to align PUC and key modifiable attributes during product development: sustained (≤1 year) delivery of novel ARV, polymers designed to optimize biodegradation timescales, incorporation of end-user acceptability information into a Target Product Profile (TPP), and evaluation of efficacy in nonhuman primate model. The AMBER program is milestone-driven and provides defined deliverables to product development efforts to support future needs in clinical translation.