title: Platelet-leucocyte adhesion markers before and after the initiation of antiretroviral therapy with HIV protease inhibitors.
abstract: BACKGROUND
  Thromboembolic complications under antiretroviral therapy (ART) have been described in the past. In particular, the influence of protease inhibitors (PIs) on platelet activation and coagulation is currently under discussion.
  
  
  METHODS
  HIV-1-infected, PI-naive adults (n = 18) were investigated before and 4 weeks after the start of the ART, consisting either of boosted PI regimens (n = 13) plus reverse transcriptase inhibitors (RTIs) or a double PI regimen (n = 5) without RTI co-medication. Administered PIs were saquinavir (n = 15), lopinavir (n = 4), fosamprenavir (n = 2) and atazanavir (n = 2). Platelet CD62P, CD40L (%+ cells) and PAC-1 binding [mean fluorescence intensity (MFI)] as well as monocyte CD11b (MFI) and monocyte-associated CD41 (%+ cells and MFI) expression were assessed by flow cytometry with or without platelet stimulation. To investigate the influence of platelets on coagulation, the endogenous thrombin potential (ETP) [render fluorescence units (RFI)] was determined.
  
  
  RESULTS
  CD62P, PAC-1 binding and CD11b expression remained unchanged. In contrast, the mean+/-SD MFI of CD40L (from 18.2+/-9.0 to 25.5+/-10.4, P = 0.038) and CD41 (from 446.1+/-213.8 to 605.0+/-183.8, P = 0.010) as markers for increased platelet-leucocyte interaction increased significantly. The collagen-induced ETP time-to-peak was altered significantly from 23.8+/-11.4 to 17.0+/-4.2 min (P = 0.028), although the ETP RFI peak showed no evidence for increased procoagulatory capacity (47.1+/-18.6 to 57.3+/-19.9, P = 0.085).
  
  
  CONCLUSIONS
  Effects of the evaluated PI HIV therapy on platelet function assessed under field conditions seem to be minor, not affecting all investigated parameters. We found no evidence for increased platelet activation under PI-containing ART. However, CD41 as a marker for increased platelet-leucocyte interaction and CD40L, which can contribute to atherosclerosis, increased significantly.
authors.affiliation: Pharmazentrum Frankfurt, Institute of Clinical Pharmacology, Johann Wolfgang Goethe University, Frankfurt, Germany. hentig@em.uni-frankfurt.de
authors.forename: Nils
authors.initials: N
authors.lastname: von Hentig
authors.forename: Ann-Kristin
authors.initials: AK
authors.lastname: Förster
authors.forename: Karina
authors.initials: K
authors.lastname: Kuczka
authors.forename: Ute
authors.initials: U
authors.lastname: Klinkhardt
authors.forename: Stefan
authors.initials: S
authors.lastname: Klauke
authors.forename: Peter
authors.initials: P
authors.lastname: Gute
authors.forename: Schlomo
authors.initials: S
authors.lastname: Staszewski
authors.forename: Sebastian
authors.initials: S
authors.lastname: Harder
authors.forename: Jochen
authors.initials: J
authors.lastname: Graff