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

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.