The objective of the study was to develop a nanocarrier-based drug delivery system that permits the loading of multiple diverse anti-HIV agents and specific targeting to HIV reservoir cells and tissues in vivo to address the major clinical hurdles in the shock and kill strategy. We first developed several strategies to load different LRAs into our hybrid nanocarriers, characterized the performance of every single formulation, and determined the best drug combination in an HIV latency cell line model. We further confirmed their latency reversal in CD4+ T cells from virologically suppressed patient, a more clinically relevant model. Next, we evaluated CD4+ T cell–specific activation in NHP PBMCs ex vivo. We used C57BL/6J mice to evaluate the in vivo targeting properties of our optimized nanocarriers, especially the ability to target and activate CD4+ T cells in LNs and their toxicity profile after subcutaneous administration. Sample sizes were chosen to detect statistical significance. Statistical analysis is detailed in the last section.

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