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 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.
De Milito
A
A
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
Hejdeman
B
B
Albert
J
J
Aleman
S
S
Sönnerborg
A
A
Zazzi
M
M
Chiodi
F
F
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008137:Longitudinal Studies; D016555:Matched-Pair Analysis; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D013997:Time Factors; D014766:Viremia; D014779:Virus Replication / Q000187:drug effects; D019014:fas Receptor / Q000097:blood*
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019014:fas Receptor