TY - JOUR T1 - Modeling Latently Infected Cell Activation: Viral and Latent Reservoir Persistence, and Viral Blips in HIV-infected Patients on Potent Therapy A1 - Rong, Libin A1 - Perelson, Alan S. Y1 - 2009/10/16 N2 - Author Summary Current combination therapy can suppress viral loads in HIV-1-infected individuals to below the detection limit of standard commercial assays. However, it cannot eradicate the virus from patients. HIV-1 can generally be identified in resting memory CD4+ T cells and persists in patients on potent treatment for a long time. These latently infected cells decay slowly, but can produce new virions when activated by relevant antigens. Many patients experience transient episodes of viremia, or blips, even though they have “undetectable” plasma viral loads for many years. Here, we develop a new mathematical model describing latently infected cell activation upon random antigenic stimulation. Using the model, we show that programmed expansion and contraction of latently infected cells upon activation can generate both low viral load persistence and viral blips. Occasional replenishment of the latent reservoir may explain the different decay kinetics of the reservoir observed in clinical practice. We also show that a model with homeostatic proliferation of latently infected cells can explain persistence of low-level virus, stability of the latent reservoir, and emergence of viral blips. These results provide novel insights into the long-term virus dynamics and could have implications for the treatment of HIV-1 infection. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 5 IS - 10 UR - https://doi.org/10.1371/journal.pcbi.1000533 SP - e1000533 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1000533 ER -