A piecewise model of virus-immune system with two thresholds

Area of Science:

• * Mathematical modeling
• * Immunology
• * Virology

Background:

• * Combined antiretroviral therapy (cART) and interleukin-2 (IL-2) may not fully restore immune response or control HIV replication.
• * Challenges remain in inducing HIV-specific immune responses and controlling viral loads with additional immune therapies.

Purpose of the Study:

• * To propose a piecewise virus-immune model with two thresholds for HIV-1 RNA and effector cell-guided therapy.
• * To analyze the dynamics of HIV-1 RNA and effector cell interactions under different therapeutic strategies.
• * To compare the efficacy of single-threshold versus two-threshold therapy strategies for HIV management.

Main Methods:

• * Development and analysis of a piecewise mathematical model simulating HIV-1 RNA and effector cell dynamics.
• * Investigation of system dynamics with effector cell-guided immune therapy, including critical intensity levels.
• * Global dynamics analysis to determine stability (stable equilibrium, bistability with periodic solutions, or virus-free periodic solutions).

Main Results:

• * A critical level of immune therapy intensity was identified for controlling HIV-1 RNA levels.
• * The model demonstrated that HIV viral loads can be eradicated, stabilized, or increase indefinitely based on threshold levels and initial conditions.
• * Two-threshold therapy strategies were shown to either eradicate the virus or expand the controllable region for maintaining low viral loads compared to single-threshold strategies.

Conclusions:

• * The proposed two-threshold model offers a framework for understanding and optimizing HIV therapy strategies.
• * Immune-guided therapy, particularly with two thresholds, can significantly impact HIV viral dynamics and immune restoration.
• * Optimized threshold settings in therapy could lead to improved HIV eradication or sustained viral load suppression.