title: HIV patients treated with low-dose prednisolone exhibit lower immune activation than untreated patients.
abstract: BACKGROUND
  HIV-associated general immune activation is a strong predictor for HIV disease progression, suggesting that chronic immune activation may drive HIV pathogenesis. Consequently, immunomodulating agents may decelerate HIV disease progression.
  
  
  METHODS
  In an observational study, we determined immune activation in HIV patients receiving low-dose (5 mg/day) prednisolone with or without highly-active antiretroviral therapy (HAART) compared to patients without prednisolone treatment. Lymphocyte activation was determined by flow cytometry detecting expression of CD38 on CD8(+) T cells. The monocyte activation markers sCD14 and LPS binding protein (LBP) as well as inflammation markers soluble urokinase plasminogen activated receptor (suPAR) and sCD40L were determined from plasma by ELISA.
  
  
  RESULTS
  CD38-expression on CD8+ T lymphocytes was significantly lower in prednisolone-treated patients compared to untreated patients (median 55.40% [percentile range 48.76-67.70] versus 73.34% [65.21-78.92], p = 0.0011, Mann-Whitney test). Similarly, we detected lower levels of sCD14 (3.6 μg/ml [2.78-5.12] vs. 6.11 μg/ml [4.58-7.70]; p = 0.0048), LBP (2.18 ng/ml [1.59-2.87] vs. 3.45 ng/ml [1.84-5.03]; p = 0.0386), suPAR antigen (2.17 μg/ml [1.65-2.81] vs. 2.56 μg/ml [2.24-4.26]; p = 0.0351) and a trend towards lower levels of sCD40L (2.70 pg/ml [1.90-4.00] vs. 3.60 pg/ml [2.95-5.30]; p = 0.0782). Viral load in both groups was similar (0.8 × 105 ng/ml [0.2-42.4 × 105] vs. 1.1 × 105 [0.5-12.2 × 105]; p = 0.3806). No effects attributable to prednisolone were observed when patients receiving HAART in combination with prednisolone were compared to patients who received HAART alone.
  
  
  CONCLUSIONS
  Patients treated with low-dose prednisolone display significantly lower general immune activation than untreated patients. Further longitudinal studies are required to assess whether treatment with low-dose prednisolone translates into differences in HIV disease progression.
authors.affiliation: University of Wuerzburg, Institute of Virology und Immunobiology, 97078 Wuerzburg, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Kasang
authors.forename: Albrecht
authors.initials: A
authors.lastname: Ulmer
authors.forename: Norbert
authors.initials: N
authors.lastname: Donhauser
authors.forename: Barbara
authors.initials: B
authors.lastname: Schmidt
authors.forename: August
authors.initials: A
authors.lastname: Stich
authors.forename: Hartwig
authors.initials: H
authors.lastname: Klinker
authors.forename: Samuel
authors.initials: S
authors.lastname: Kalluvya
authors.forename: Eleni
authors.initials: E
authors.lastname: Koutsilieri
authors.forename: Axel
authors.initials: A
authors.lastname: Rethwilm
authors.forename: Carsten
authors.initials: C
authors.lastname: Scheller
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000209:Acute-Phase Proteins / Q000032:analysis; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage; D023201:CD40 Ligand / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology; D002352:Carrier Proteins / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D016130:Immunophenotyping; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000276:immunology; D011239:Prednisolone / Q000008:administration & dosage*; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D051997:ADP-ribosyl Cyclase 1; D000209:Acute-Phase Proteins; D019380:Anti-HIV Agents; D023201:CD40 Ligand; D002352:Carrier Proteins; D007155:Immunologic Factors; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D011239:Prednisolone; D055293:Receptors, Urokinase Plasminogen Activator; D000099231:Lipopolysaccharide-Binding Protein; C524898:PLAUR protein, human; C498154:CD38 protein, human