‘Rinse and Replace’: Boosting T Cell Turnover To Reduce HIV-1 Reservoirs

Latent HIV-1 persists indefinitely during antiretroviral therapy (ART) as an integrated silent genome in long-lived memory CD4⁺ T cells. In untreated infections, immune activation increases the turnover of intrinsically long-lived provirus-containing CD4⁺ T cells. Those are ‘washed out’ as a result of their activation, which when coupled to viral protein expression can facilitate local inflammation and recruitment of uninfected cells to activation sites, causing latently infected cells to compete for survival. De novo infection can counter this washout. During ART, inflammation and CD4⁺ T cell activation wane, resulting in reduced cell turnover and a persistent reservoir. We propose accelerating reservoir washout during ART by triggering sequential waves of polyclonal CD4⁺ T cell activation while simultaneously enhancing virus protein expression. Reservoir reduction as an adjunct to other therapies might achieve lifelong viral control.