Platelet–leucocyte adhesion markers before and after the initiation of antiretroviral therapy with HIV protease inhibitors

• Published in: Journal of antimicrobial chemotherapy 2008-11, Vol.62 (5), p.1118-1121
• Main Authors: von Hentig, Nils, Förster, Ann-Kristin, Kuczka, Karina, Klinkhardt, Ute, Klauke, Stefan, Gute, Peter, Staszewski, Schlomo, Harder, Sebastian, Graff, Jochen
• Format: Article
• Language: English
• Subjects: Adult; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral drugs; Biological and medical sciences; Blood Platelets - chemistry; Blood Platelets - drug effects; CD11b Antigen - analysis; CD40 Ligand - analysis; CD40L; CD41; Cell Adhesion Molecules - biosynthesis; Drug therapy; Female; Flow Cytometry; HIV; HIV Infections - drug therapy; HIV PIs; HIV Protease Inhibitors - adverse effects; HIV Protease Inhibitors - therapeutic use; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; leucocytes; Leukocytes; Leukocytes - chemistry; Leukocytes - drug effects; Male; Medical sciences; Middle Aged; Molecular biology; P-Selectin - analysis; Pharmacology. Drug treatments; Platelet Membrane Glycoprotein IIb - analysis; platelets; Protease inhibitors; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkn333

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.