High plasma levels of soluble Fas in HIV type 1-infected subjects are not normalized during highly active antiretroviral therapy

Plasma levels of soluble Fas (sFas) are elevated in human immunodeficiency virus type 1 (HIV-1) infection, indicating dysregulation of the Fas apoptos is pathway and chronic immune activation. We performed a retrospective stud y to investigate the effects of HAART on plasma levels of sFas. A cross-sec tional study of 27 drug-naive infected subjects and 49 patients under antir etroviral treatment showed that plasma levels of sFas were higher in HIV-1- infected subjects than in 52 HIV-1-negative controls, independently of the treatment status. In a longitudinal study of 69 patients undergoing HAART, we observed a minimal, but significant decrease in sFas plasma levels after 1 year of therapy. Levels of sFas, however, remained still higher than phy siologic values. Patients undergoing HAART were further classified as nonre sponders or responders on the basis of viremia suppression; no significant changes in plasma levels of sFas were observed between the two groups. Thes e findings show that 1 year of HAART has a minor effect on the sFas levels in plasma. Longterm HAART may be required to normalize the dysregulation of the Fas apoptotic pathway and the persistent immune activation initiated b y HIV-1.