Platelet decline: An avenue for investigation into the pathogenesis of human immunodeficiency virus-associated dementia

Lynn M. Wachtman, Richard Skolasky, Patrick Tarwater, Deneen Esposito, Giovanni Schifitto, Karen Marder, Michael P. McDermott, Bruce A. Cohen, Avindra Nath, Ned Sacktor, Leon G. Epstein, Joseph L Mankowski, Justin Charles McArthur

Research output: Contribution to journalArticle

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. Design: Prospective cohort study within the North-East AIDS Dementia cohort. Setting: Four participating referral centers in the United States. Participants: 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/μL or less than 300/μL 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.

Original languageEnglish (US)
Pages (from-to)1264-1272
Number of pages9
JournalArchives of Neurology
Volume64
Issue number9
DOIs
StatePublished - Sep 2007

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Dementia
Blood Platelets
HIV
Confidence Intervals
AIDS/HIV
Virus Diseases
CD4 Lymphocyte Count
Platelet Count
Nervous System
Acquired Immunodeficiency Syndrome
Cohort Studies
Referral and Consultation
Biomarkers
Outcome Assessment (Health Care)
Prospective Studies

ASJC Scopus subject areas

  • Neuroscience(all)

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Platelet decline : An avenue for investigation into the pathogenesis of human immunodeficiency virus-associated dementia. / Wachtman, Lynn M.; Skolasky, Richard; Tarwater, Patrick; Esposito, Deneen; Schifitto, Giovanni; Marder, Karen; McDermott, Michael P.; Cohen, Bruce A.; Nath, Avindra; Sacktor, Ned; Epstein, Leon G.; Mankowski, Joseph L; McArthur, Justin Charles.

In: Archives of Neurology, Vol. 64, No. 9, 09.2007, p. 1264-1272.

Research output: Contribution to journalArticle

Wachtman, Lynn M. ; Skolasky, Richard ; Tarwater, Patrick ; Esposito, Deneen ; Schifitto, Giovanni ; Marder, Karen ; McDermott, Michael P. ; Cohen, Bruce A. ; Nath, Avindra ; Sacktor, Ned ; Epstein, Leon G. ; Mankowski, Joseph L ; McArthur, Justin Charles. / Platelet decline : An avenue for investigation into the pathogenesis of human immunodeficiency virus-associated dementia. In: Archives of Neurology. 2007 ; Vol. 64, No. 9. pp. 1264-1272.
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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. Design: Prospective cohort study within the North-East AIDS Dementia cohort. Setting: Four participating referral centers in the United States. Participants: 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/μL or less than 300/μL 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.",
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AU - Tarwater, Patrick

AU - Esposito, Deneen

AU - Schifitto, Giovanni

AU - Marder, Karen

AU - McDermott, Michael P.

AU - Cohen, Bruce A.

AU - Nath, Avindra

AU - Sacktor, Ned

AU - Epstein, Leon G.

AU - Mankowski, Joseph L

AU - McArthur, Justin Charles

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