[C16] Infectious Diseases

[C16-01] Quantitative analysis of effectiveness of latency reversing agent (LRA) with HIV-Tocky system

*Morihiko Mizuno¹, Yorifumi Sato², Kosaku Kitagawa¹, Shingo Iwami¹ (1. Nagoya University (Japan), 2. Kumamoto University (Japan))

Keywords:

HIV

Acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV), has remained a globally prevalent infectious disease since its emergence in the late 20th century. Although combination antiretroviral therapy (ART), introduced in the mid-1990s, enables long-term viral suppression, complete eradication of HIV is hindered by the persistence of latently infected cells. These cells evade immune surveillance and drug-mediated clearance, forming long-lived reservoirs that necessitate lifelong treatment.The "Shock and Kill" strategy seeks to eliminate these reservoirs by employing latency-reversing agents (LRAs) to reactivate dormant infected cells, thereby rendering them susceptible to ART. However, a quantitative framework for assessing LRA efficacy within the context of viral dynamics has yet to be established.In this study, we developed a mathematical model to quantify the effects of LRAs using experimental data derived from the HIV-Tocky system. By integrating a timer fluorescent protein into HIV, we monitored the infection status via time-dependent fluorescence changes, which enabled the collection of time-series data on infected cells. For analytical simplicity, we classified infected cells into four groups based on fluorescence intensity and color, and constructed a mathematical model that recapitulates the transitions between these groups. This model allowed us to quantitatively assess changes in the activation rate of latently infected cells in the presence and absence of LRAs.Our analysis demonstrates that LRAs significantly enhance the activation of latently infected cells, and the corresponding infection parameters can be quantitatively evaluated. These findings suggest that the integration of the HIV-Tocky system with mathematical modeling provides a high-resolution approach for elucidating the mechanisms and temporal effects of LRAs, thereby advancing the "Shock and Kill" strategy.