Reconstitution of thymic function in HIV-1 patients treated with highly active antiretroviral therapy

Abstract

The extent to which highly active antiretroviral therapy can restore thymic function in HIV-1 infected patients is not known. We simulate treatment using a temporal model of thymopoiesis during HIV-1 infection, tracking thymic function by the number of recent thymic emigrants (RTE) exported to the periphery per day. Our results suggest that suppressing viral load in peripheral blood and improving inherent thymic function are necessary for the reconstitution of RTE levels in adult thymic infection with either R5 or X4 HIV-1 strains. This is also the case in pediatric thymic infection with R5 strains. However, recovery of RTE levels during pediatric infection with X4 strains also depends on high drug efficacy within the thymus. We further predict that protease inhibitors have high levels of efficacy directly suppressing viral replication within the thymus, while reverse transcriptase inhibitors have low efficacy.