T-cell progenitor function during progressive human immunodeficiency virus-1 infection and after antiretroviral therapy

Impairment of T-cell renewal has been proposed as contributing to CD4(+) T- cell depletion in persons infected with human immunodeficiency virus-1. We analyzed the T-cell development capacity of progenitors using fetal thymus organ culture. Those who progressed to AIDS had a dramatic loss in T-cell d evelopment capacity shortly after seroconversion. In contrast, long-term no nprogressors retained progenitor capacity 8 years after seroconversion. App roximately 70% of patients experienced an improvement in T-cell development capacity after receiving 6 months of potent antiretroviral therapy. Improv ement in T-cell development in fetal thymus organ culture correlated with a n increase in the number of naive CD4(+) T cells in peripheral blood. Numbe rs of progenitors in blood and bone marrow after seroconversion or during t herapy did not correlate with the change observed in T-cell development cap acity. These data provide evidence that HIV-1 infection can interfere with T-cell renewal at the level of the progenitor cell. Interference with T-cel l renewal may contribute to CD4(+) T-cell depletion. (Blood. 2000;96:242-24 9) (C) 2000 by The American Society of Hematology.