title: Reduced platelet hyperreactivity and platelet-monocyte aggregation in HIV-infected individuals receiving a raltegravir-based regimen.
abstract: OBJECTIVE
  Platelets are key cells in atherosclerosis and acute cardiovascular events. Platelet hyperreactivity and increased platelet-monocyte aggregation (PMA) are found in HIV-infected patients and may contribute to the excess cardiovascular risk. The integrase inhibitor raltegravir (RAL) has been associated with better residual viral suppression and reduction in inflammatory and coagulation biomarkers. The aim of our study was to investigate whether RAL-treated patients have reduced platelet reactivity and PMA.
  
  
  METHODS
  We performed a cross-sectional study involving 80 virologically suppressed adult HIV1-infected patients on a RAL-based (n = 25), nonnucleoside reverse transcriptase inhibitor (NNRTI)-based (n = 30) or a protease inhibitor based (n = 25) regimen and 30 healthy controls. Platelet reactivity was determined by measuring platelet P-selectin expression and the binding of fibrinogen to platelets to stimulation with two concentrations of ADP. PMA was determined by measuring the expression of the platelet marker CD42b on CD14 positive cells.
  
  
  RESULTS
  HIV-infected individuals had higher platelet reactivity and PMA than controls. RAL-treated individuals showed significantly lower P-selectin expression to stimulation with low (P = 0.026 vs. NNRTI and P = 0.005 vs. protease inhibitor group) and high-dose ADP (P = 0.009 vs. NNRTI and P = 0.003 vs. protease inhibitor group). A similar trend for was found for fibrinogen binding, although only the difference in P-selectin expression between RAL and protease inhibitor treated patients reached statistical significance (P = 0.038). PMA was also lower in the RAL group than in the NNRTI (P = 0.037) and protease inhibitor (P = 0.034) groups.
  
  
  CONCLUSIONS
  Use of a RAL-based regimen was associated with a reduction in persistent HIV-induced platelet hyperreactivity and PMA compared with NNRTI and protease inhibitor based regimen.
authors.affiliation: aDepartment of Internal Medicine, Radboud university medical center, Nijmegen, The Netherlands bCenter for Tropical and Infectious Disease (CENTRID), Faculty of Medicine Diponegoro University, Dr Kariadi Hospital, Semarang, Indonesia cDepartment of Clinical Chemistry and Haematology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Rahajeng N
authors.initials: RN
authors.lastname: Tunjungputri
authors.forename: Andre J
authors.initials: AJ
authors.lastname: Van Der Ven
authors.forename: Anna
authors.initials: A
authors.lastname: Schonsberg
authors.forename: Till S
authors.initials: TS
authors.lastname: Mathan
authors.forename: Peter
authors.initials: P
authors.lastname: Koopmans
authors.forename: Mark
authors.initials: M
authors.lastname: Roest
authors.forename: Rob
authors.initials: R
authors.lastname: Fijnheer
authors.forename: Philip G D E
authors.initials: PG
authors.lastname: Groot
authors.forename: Quirijn
authors.initials: Q
authors.lastname: de Mast
mesh_terms: D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D019007:P-Selectin / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011760:Pyrrolidinones / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D011760:Pyrrolidinones; D018894:Reverse Transcriptase Inhibitors; D000068898:Raltegravir Potassium