An HIV model with age-structured latently infected cells

Area of Science:

• Virology
• Mathematical Biology
• Immunology

Background:

• Human immunodeficiency virus (HIV) latency is a significant barrier to complete viral eradication.
• The rate at which latently infected cells activate may be influenced by the duration of the latent infection.

Purpose of the Study:

• To develop and analyze a mathematical model of HIV infection that incorporates age-structured latently infected cells.
• To investigate how age-dependent activation rates affect viral persistence and latent reservoir stability in patients on therapy.

Main Methods:

• Mathematical analysis of an age-structured HIV infection model.
• Numerical simulations using various activation functions.
• Sensitivity analysis of model parameters.
• Extension of the model to include homeostatic proliferation of latently infected cells.

Main Results:

• The model successfully explains the persistence of low-level viremia and the stability of the latent reservoir in patients undergoing therapy.
• Model sensitivity is low for most parameters but high for the balance between net generation rate and long-term activation rate.
• The extended model, incorporating homeostatic proliferation, demonstrates robustness in replicating long-term viral and latent cell dynamics in patients on prolonged combination therapy.

Conclusions:

• Age-structuring of the latent reservoir is crucial for understanding HIV persistence during therapy.
• Mathematical modeling provides valuable insights into HIV dynamics and reservoir stability.
• Further model refinement, including homeostatic proliferation, enhances its ability to predict long-term viral behavior in treated patients.