Positive feedback through inflammation creates bistable behavior in HIV tissue sanctuaries

Area of Science:

• Mathematical Biology
• Immunology
• Virology

Background:

• Combination Antiretroviral Therapy (cART) effectively suppresses HIV in blood plasma.
• Previous research suggests persistent HIV replication in inflamed lymph node sanctuaries despite cART.
• Inflammation is identified as a critical factor for ongoing HIV replication in these sites.

Purpose of the Study:

• To model the hypothesis that ongoing HIV replication can sustain inflammation within lymph node follicles.
• To investigate the dynamics of HIV replication and inflammation in lymph node sanctuary sites.
• To understand how these dynamics lead to distinct steady-state outcomes.

Main Methods:

• Utilized a system of ordinary differential equations coupled with a reactive-diffusion system.
• Modeled HIV dynamics and lymph node follicle diameter over time.
• Incorporated parameter estimates from prior data where available.

Main Results:

• Identified two stable steady-state solutions: one with low inflammation and no replication, and another with high inflammation and significant replication.
• Demonstrated that the system can transition between these states.
• Showed that a transient pro-inflammatory stimulus can trigger a shift towards the high-replication state.

Conclusions:

• Ongoing HIV replication within lymph node sanctuaries can create a self-sustaining inflammatory loop.
• The spatial isolation of these sites contributes to low plasma viral loads, masking persistent replication.
• These findings highlight the complexity of HIV persistence and the potential for viral rebound.