Despite significant progress in the global fight against HIV/AIDS, the disease is still a serious public health problem around the globe. Current ARV therapy (ART) has transformed HIV into a chronic illness from a death sentence; however, limitations such as low drug bioavailability, off-target toxicity, resistant strain development, and the presence of latent viral reservoirs are still major hurdles to elimination. In the last few years, nanochitosan (NCH) has gained increasing attention as a multifunctional and biocompatible nanomaterial with the promise of fulfilling these unmet clinical demands. Its inherent properties of mucoadhesion, antimicrobial activity, biodegradability, and immunomodulation place NCH in the most suitable position as a prospective agent for HIV prevention and treatment. NCH could serve as a carrier for directed and controlled delivery of antiretroviral (ARV) agents, enhance residence time at mucosal sites, and increase penetration through biological barriers to augment therapeutic effectiveness and minimize systemic toxicity. Its cationic properties also allow direct interaction with the viral envelope's negative charge, potentially inhibiting viral entry and replication. This review critically examines recent advances in NCH-based approaches, including prophylactic products such as intravaginal gels and films, targeted ART delivery systems for latent reservoirs, and new insights into NCH's direct antiviral activity. Lastly, the potential role of mathematical modeling in predicting viral load behavior and in justifying dosing regimens quantitatively is debated. Translational hurdles of paramount concern, e.g., large-scale production, long-term safety, regulatory approval, and cost-effectiveness, are also addressed. By uniting nanotechnology, virology, and systems pharmacology, this article positions NCH as a next-generation platform capable of revolutionizing HIV prevention and treatment worldwide
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