Search

Plasma levels of soluble Fas (sFas) are elevated in human immunodeficiency virus type 1 (HIV-1) infection, indicating dysregulation of the Fas apoptosis pathway and chronic immune activation. We performed a retrospective study to investigate the effects of HAART on plasma levels of sFas. A cross-sectional study of 27 drug-naive infected subjects and 49 patients under antiretroviral 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 physiologic values. Patients undergoing HAART were further classified as nonresponders or responders on the basis of viremia suppression; no significant changes in plasma levels of sFas were observed between the two groups. These findings show that 1 year of HAART has a minor effect on the sFas levels in plasma. Long-term HAART may be required to normalize the dysregulation of the Fas apoptotic pathway and the persistent immune activation initiated by HIV-1.

Methods We have expressed the soluble form of the HIV envelope of the C/B’ strain 97/CN/54 in CHO cells. The production process consisted of a large-scale fed-batch fermentation, an antibody-based affinity chromatography plus additional purifying steps. CN54gp140 was extensively characterized for purity and identity. All glycosylation sites were characterized by mass spectrometry. Immunogenicity and safety were evaluated in mice, rabbits, minipigs, sheep as well as non-human primates. The antigen was formulated for clinical phase I studies in Tris buffer (MUCOVAC I, HIVIS07) in HEC gel (MUCOVAC I) as well as chemically conjugated to hsp70 (MUVAPRED).