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An Avenue for Investigation Into the Pathogenesis of Human Immunodeficiency Virus–Associated Dementia

Lynn M. Wachtman, DVM, MPH; Richard L. Skolasky, MA; Patrick M. Tarwater, PhD; Deneen Esposito, BA; Giovanni Schifitto, MD; Karen Marder, MD, MPH; Michael P. McDermott, PhD; Bruce A. Cohen, MD; Avindra Nath, MD; Ned Sacktor, MD; Leon G. Epstein, MD; Joseph L. Mankowski, DVM, PhD; Justin C. McArthur, MBBS, MPH

Arch Neurol. 2007;64(9):1264-1272.

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.

Author Affiliations: Departments of Molecular and Comparative Pathobiology (Drs Wachtman and Mankowski), Orthopedics (Mr Skolasky), Neurology (Ms Esposito and Drs Nath, Sacktor, and McArthur), and Pathology (Drs Mankowski and McArthur), School of Medicine, and Department of Epidemiology, Bloomberg School of Public Health (Dr McArthur), The Johns Hopkins University, Baltimore, Maryland; Department of Biostatistics and Epidemiology, The University of Texas Health Science Center at Houston, School of Public Health, El Paso Regional Campus (Dr Tarwater); Departments of Neurology (Drs Schifitto and McDermott) and Biostatistics and Computational Biology (Dr McDermott), University of Rochester Medical Center, Rochester, New York; Department of Neurology, Columbia University, New York, New York (Dr Marder); and Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (Drs Cohen and Epstein). Dr Wachtman is now with the New England Primate Research Center, Harvard Medical School, Southboro, Massachusetts.

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