Modeling how memory CD8 T cells can elicit post-treatment control of HIV infection

While most individuals living with HIV experience progressive disease after stopping antiretroviral therapy, a small percentage achieve lasting control post-treatment. Grasping the mechanisms behind this control is crucial for developing effective HIV remission strategies. Recent research suggests memory CD8 T cells play a role, but the precise process remains unclear.

To shed light on this, we combined mathematical modeling with data from SIV-infected non-human primates. Our findings indicate that ongoing antigenic stimulation results in permanent changes in the CD8 T cell pool, which hinders memory cell survival. Antiretroviral therapy swiftly reduces viral load, halting antigenic stimulation and maintaining memory potential.

The extent of this preservation directly impacts the recall response upon viral rebound following treatment. Our mathematical model, based on this hypothesis, suggests that post-treatment control represents an alternative steady state to progressive infection, achieved through robust memory-driven recall responses. When validated against longitudinal virological data encompassing pre-, during-, and post-antiretroviral treatment phases, the model aligns with both progressive disease outcomes and long-term remission, particularly when treatment begins early.

It reveals that memory CD8 T cells can independently drive post-treatment control, irrespective of the size of the latent viral reservoir. This finding contradicts prevalent hypotheses that rely on reservoir size. Moreover, our model identifies a specific time window for initiating treatment that maximizes the likelihood of post-treatment control.

Ultimately, our model's predictions provide valuable insights for designing interventions aimed at targeting memory CD8 T cells to achieve HIV remission.