Low Platelet Count – High Risk Of HIV-related Dementia
HIV patients with declining platelet counts appear to be at increased risk for HIV–associated dementia.
“Human immunodeficiency virus–associated dementia (HIV-D) is a syndrome encompassing a spectrum of cognitive, behavioral and motor deficits that usually has an insidious onset and a chronic progressive course,” the authors write as background information in the article. Therapies leading to longer life for HIV patients have paradoxically increased the prevalence of this condition. Identifying biological markers for the development of HIV–associated dementia is critical both for diagnosing the disorder and for understanding its underlying mechanisms.
Lynn M. Wachtman, D.V.M., M.P.H., of Bloomberg School of Public Health, The Johns Hopkins University School of Medicine, Baltimore, and colleagues studied 396 patients with advanced HIV who were recruited for this prospective study between 1998 and 2003. Participants were examined every six months and completed mental and physical evaluations.
Blood samples were also collected and assessed for platelet count (the number of clotting cells in the blood), hemoglobin levels, CD4 lymphocyte count (a measure of certain types of white blood cells, which reflects the state of the immune system) and plasma HIV RNA levels (which indicate the amount of “viral load,” and predict HIV progression).
After a median (midpoint) follow-up of 31.1 months, 40 participants developed HIV–associated dementia. A decline in platelet count from baseline was associated with the development of dementia within six to 12 months. “Those HIV-infected individuals with a decline in platelets from baseline values at this lagged time point had a two-fold increased risk of dementia” in several different analyses, the authors write. The specific timing of the association indicates that the levels of circulating platelets fluctuate as HIV–associated dementia develops, they note.
“Further analyses indicated that decline from baseline platelet levels was associated with a five- to six-fold increased risk of dementia during the first two years of follow-up, but it was not associated with an increased risk of dementia after two years,” the authors continue. “It is possible that individuals who do not progress rapidly to neurologic compromise differ in respect to immune activation, treatment adherence or virologic control relative to those who develop dementia more rapidly.”
“Because CD4 cell counts and HIV RNA levels have proven not to be predictive of HIV–associated dementia, it is important to investigate alternative serum and hematologic markers,” the authors conclude. “Should these markers be routinely measured in a clinical setting, such as platelet counts, they may prove useful for patient management. This study identifies a significant association between platelet decline and incident HIV–associated dementia.” Further study of platelet levels during HIV–associated dementia may lead both to a specific marker for the development of HIV–associated dementia and a better understanding of how the disease develops.
Arch Neurol. 2007 Sep;64(9):1264-72.
Platelet decline: an avenue for investigation into the pathogenesis of human immunodeficiency virus associated dementia.
Department of Neurology, The Johns Hopkins University School of Medicine, 600 N Wolfe St, Baltimore, MD 21287-7609. email@example.com.
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/muL or less than 300/muL 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.