title: Platelet count kinetics following interruption of antiretroviral treatment.
abstract: OBJECTIVE
  To investigate the mechanisms of platelet kinetics in the Strategies for Management of Antiretroviral Therapy (SMART) study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) drug conservation compared with continuous treatment viral suppression. Follow-up analyses of stored plasma samples demonstrated increased activation of both inflammatory and coagulation pathways after stopping ART.
  
  
  METHODS
  SMART patients from sites that determined platelets routinely.
  
  
  METHODS
  Platelet counts were retrospectively collected from 2206 patients from visits at study entry, and during follow-up. D-dimer levels were measured at study entry, month 1, and 2.
  
  
  RESULTS
  Platelet levels decreased in the drug conservation group following randomization, but remained stable in the viral suppression group [median (IQR) decline from study entry to month 4: -24 000/μl (-54 000 to 4000) vs. 3000 (-22 000 to 24 000), respectively, P < 0.0001)] and the rate of developing thrombocytopenia (<100 000/μl) was significantly higher in the drug conservation vs. the viral suppression arm (unadjusted drug conservation/viral suppression [HR (95%CI) = 1.8 (1.2-2.7)]. The decline in platelet count among drug conservation participants on fully suppressive ART correlated with the rise in D-dimer from study entry to either month 1 or 2 (r = -0.41; P = 0.02). Among drug conservation participants who resumed ART 74% recovered to their study entry platelet levels.
  
  
  CONCLUSIONS
  Interrupting ART increases the risk of thrombocytopenia, but reinitiation of ART typically reverses it. Factors contributing to declines in platelets after interrupting ART may include activation of coagulation pathways or HIV-1 replication itself. The contribution of platelets in HIV-related procoagulant activity requires further study.
authors.affiliation: Copenhagen University Hospital/Rigshospitalet and University of Copenhagen, Denmark.
authors.forename: Eva
authors.initials: E
authors.lastname: Zetterberg
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Neuhaus
authors.forename: Jason V
authors.initials: JV
authors.lastname: Baker
authors.forename: Charurut
authors.initials: C
authors.lastname: Somboonwit
authors.forename: Josep M
authors.initials: JM
authors.lastname: Llibre
authors.forename: Adrian
authors.initials: A
authors.lastname: Palfreeman
authors.forename: Maria
authors.initials: M
authors.lastname: Chini
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000097:blood; D000933:Antifibrinolytic Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006679:HIV Seropositivity / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D007249:Inflammation / Q000097:blood; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016896:Treatment Outcome; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D000933:Antifibrinolytic Agents; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D