A Novel Entomovirological Approach to Eradicating HIV: Integrating Insect-Derived Vectors, Microbiome Engineering, and CRISPR-Based Gene Therapy for Complete AIDS Cure

This conceptual manuscript delineates a pioneering therapeutic paradigm for the sterilizing eradication of HIV/AIDS, synergistically amalgamating insights from entomology, microbiology, virology, cellular biology, genetic engineering, and immunology. We posit a novel entomovirological vector, engineered from insect viruses such as baculoviruses, to deliver CRISPR-Cas9 systems precisely targeting HIV proviral DNA, concomitant with gut microbiome modulation to augment immune responses and preclude viral rebound. Feasibility is substantiated through rigorous mathematical modeling, encompassing extended differential equations with latency compartments, comprehensive local and global stability analyses via the next-generation matrix method and Lyapunov functions, Bayesian inference for parameter estimation in HIV dynamics, advanced sensitivity analyses including partial rank correlation coefficients (PRCC), and uncertainty quantification. Simulations, parameterized with empirical data, evince potential viral clearance to negligible levels. Enhanced graphical representations elucidate system dynamics and sensitivities. A multifaceted, empirically falsifiable roadmap, spanning preclinical to manufacturing phases with detailed experimental protocols, is delineated. This framework heralds a curative shift beyond extant antiretroviral therapies, harboring profound implications for personalized medicine and global HIV eradication.