Precision Elimination: Proof-of-Concept In Silico Testing of a Novel Construct for Optimizing HIV-1 Eradication

The persistence of latent HIV reservoirs presents a major barrier to HIV eradication. This study evaluates the effectiveness of an HIV-1 LTR-driven negative selection marker in eliminating latent and active HIV-infected cells through a combination of latency reversal and targeted cell apoptosis. Using computational modeling in NetLogo and Tellurium, two conditions were simulated: a control group receiving only combination antiretroviral therapy (cART) and latency-reversing agents (LRA), and an experimental group incorporating the marker system. The control group showed continued viral spread due to the inability of cART to target reactivated latent cells. In contrast, the experimental group demonstrated a significant reduction in HIV-infected cells, with the marker achieving an overall effectiveness of 49% in eliminating reactivated and actively infected cells. Additionally, the marker significantly reduced the spread of HIV, as indicated by a 12.5% higher number of healthy cells in the experimental group compared to the control. These results, while promising, come with inherent in silico limitations, including marker expression variability and immune system interactions. Further experimental validation is needed to assess translational feasibility.