Global Dynamics of a Dual-Target HIV Model with Time Delays and Treatment Implications

We present a comprehensive mathematical analysis of a within-host dual-target HIV dynamics model, which explicitly incorporates the virus’s interactions with its two primary cellular targets: CD4+ T cells and macrophages. The model is formulated as a system of five nonlinear delay differential equations, integrating three distinct discrete time delays to account for critical intracellular processes such as the development of productively infected cells and the maturation of new virions. We first establish the model’s biological well-posedness by proving the non-negativity and boundedness of solutions, ensuring all trajectories remain within a feasible region. The basic reproduction number, R0d, is derived using the next-generation matrix method and serves as a sharp threshold for disease dynamics. Analytical results demonstrate that the infection-free equilibrium is globally asymptotically stable (GAS) when R0d≤1, guaranteeing viral eradication from any initial state. Conversely, when R0d>1, a unique endemic equilibrium emerges and is proven to be GAS, representing a state of chronic infection. These global stability properties are rigorously established for both the non-delayed and delayed systems using carefully constructed Lyapunov functions and functionals, coupled with LaSalle’s invariance principle. A sensitivity analysis identifies viral production rates (p1,p2) and infection rates (β1,β2) as the most influential parameters on R0d, while the viral clearance rate (m) and maturation delay (τ3) have a suppressive effect. The model is extended to evaluate antiretroviral therapy (ART), revealing a critical treatment efficacy threshold ϵcr required to suppress the virus. Numerical simulations validate all theoretical findings and further investigate the dynamics under varying treatment efficacies and maturation delays, highlighting how these factors can shift the system from persistence to clearance. This study provides a rigorous mathematical framework for understanding HIV dynamics, with actionable insights for designing targeted treatment protocols aimed at achieving viral suppression.