JAC Advance Access originally published online on August 27, 2008
Journal of Antimicrobial Chemotherapy 2008 62(5):1118-1121; doi:10.1093/jac/dkn333
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Original research |
Platelet–leucocyte adhesion markers before and after the initiation of antiretroviral therapy with HIV protease inhibitors
1 Pharmazentrum Frankfurt, Institute of Clinical Pharmacology, Johann Wolfgang Goethe University, Frankfurt, Germany 2 Infektiologikum Frankfurt, Frankfurt, Germany 3 HIVCENTER, Medical HIV Treatment and Research Unit, Johann Wolfgang Goethe University, Frankfurt, Germany
Received 9 June 2008; returned 6 July 2008; revised 18 July 2008; accepted 19 July 2008
* Corresponding author. Tel: +49-69-63016956; Fax: +49-69-63017636; E-mail: hentig{at}em.uni-frankfurt.de
Introduction: 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.
Keywords: HIV PIs , platelets , leucocytes , CD40L , CD41