title: Platelet decline: an avenue for investigation into the pathogenesis of human immunodeficiency virus -associated dementia.
abstract: BACKGROUND
  The identification of biomarkers identifying onset of human immunodeficiency virus-associated dementia (HIV-D) is critical for diagnosis and the elucidation of pathophysiologic pathways.
  
  
  OBJECTIVE
  To examine the association between platelet decline from baseline and HIV-D.
  
  
  METHODS
  Prospective cohort study within the North-East AIDS Dementia cohort.
  
  
  METHODS
  Four participating referral centers in the United States.
  
  
  METHODS
  A total of 396 subjects with advanced human immunodeficiency virus (HIV) infection recruited between 1998 and 2003 and undergoing serial neurologic assessments. Eligibility criteria required CD4 cell counts less than 200/microL or less than 300/microL with evidence of cognitive impairment. A cohort subset without prevalent HIV-D at baseline and without incident HIV-D at the visit immediately after baseline was analyzed (n = 146). Main Outcome Measure Time to first diagnosis of HIV-D.
  
  
  RESULTS
  After a median follow-up of 31.1 months, 40 subjects developed HIV-D. Platelet decline from baseline was associated with the development of HIV-D when examined as a time-dependent variable lagged by 6 to 12 months before outcome (multivariate hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.14-5.02; P = .02). This association was stronger during the first 2 years of follow-up (multivariate HR, 6.76; 95% CI, 2.36-19.41; P < .001) than during later years (multivariate HR, 0.94; 95% CI, 0.33-2.67; P = .90).
  
  
  CONCLUSIONS
  These results suggest that individuals with declining platelet counts are at greater risk for HIV-D and that the dynamics of circulating platelets vary with respect to the temporal progression of HIV-D. This highlights an avenue to be explored in the understanding of HIV-D pathogenesis.
authors.affiliation: Department of Molecular and Comparative Pathobiology, The Johns Hopkins University, Baltimore, Maryland 21287-7609, USA.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Wachtman
authors.forename: Richard L
authors.initials: RL
authors.lastname: Skolasky
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Tarwater
authors.forename: Deneen
authors.initials: D
authors.lastname: Esposito
authors.forename: Giovanni
authors.initials: G
authors.lastname: Schifitto
authors.forename: Karen
authors.initials: K
authors.lastname: Marder
authors.forename: Michael P
authors.initials: MP
authors.lastname: McDermott
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Cohen
authors.forename: Avindra
authors.initials: A
authors.lastname: Nath
authors.forename: Ned
authors.initials: N
authors.lastname: Sacktor
authors.forename: Leon G
authors.initials: LG
authors.lastname: Epstein
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Mankowski
authors.forename: Justin C
authors.initials: JC
authors.lastname: McArthur
mesh_terms: D015526:AIDS Dementia Complex / Q000097:blood* / Q000473:pathology; D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers; D001792:Blood Platelets / Q000473:pathology / Q000502:physiology*; D018791:CD4 Lymphocyte Count; D003071:Cognition / Q000502:physiology; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D012367:RNA, Viral