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.
The goal of this proposed program is to develop an end-user informed HIV pre-exposure prophylaxis (PrEP) technology as an Acceptable Multi-user Biodegradable Extended Release (AMBER) implant. The AMBER implant offers the following beneficial features for delivery of novel PrEP agents: user independence, long-term protection (?1 year), and discretion of use, biodegradation, and retrievability, if needed, for the duration of drug delivery.
