EARLY T-CELL APOPTOSIS AND FAS EXPRESSION DURING ANTIRETROVIRAL THERAPY IN INDIVIDUALS INFECTED WITH HUMAN IMMUNODEFICIENCY VIRUS-1

Several lines of evidence suggest that Fas-mediated apoptosis is invol ved in the CD4 T-cell depletion in human immunodeficiency virus-1 (HIV -1) infection. To investigate this, we studied changes in peripheral b lood, early T-cell apoptosis and Fas expression after initiation of an tiretroviral therapy (ART) in 18 HIV-1-infected individuals. Flow cyto metric analysis was performed with Apostain(TM) and CD4, CD8 and Fas s taining. Fas expression was quantified by standardized beads. The leve ls of CD4 and CD8 T cells with early apoptosis were increased comparab ly in HN-1-infected individuals. Despite elevated CD4 T cell counts, n o decline in early T-cell apoptosis could be detected during the first 8 weeks of ART. However, after 26 weeks of ART in five patients that showed a sustained reduction of viral replication there was a marked d ecrease in T cells with features of early apoptosis. No difference was found for Fas express:ion on early apoptotic T cells. Fas expression on CD4 and CD8 T cells was reduced after initiation of ART; this was i ndependent of the CD4 T-cell trend and indicates that the immediate CD 4 T-cell expansion during ART is probably not the result of a decrease d rate of early apoptosis among peripheral blood CD4 T cells. However, preliminary data imply a long-term reduction of early T-cell apoptosi s and Fas expression in patients who show a sustained reduction of vir al replication.