A concise panel of biomarkers identifies neurocognitive functioning changes in HIV-infected individuals.

TitleA concise panel of biomarkers identifies neurocognitive functioning changes in HIV-infected individuals.
Publication TypeJournal Article
Year of Publication2013
AuthorsMarcotte, TD, Deutsch, R, Michael, BDaniel, Franklin, D, Cookson, DRosario, Bharti, AR, Grant, I, Letendre, S
Corporate AuthorsCHARTER Group
JournalJ Neuroimmune Pharmacol
Date Published2013 Dec
KeywordsAdult, AIDS Dementia Complex, Biomarkers, CHARTER, Female, HIV Infections, Humans, Internal, Male, Middle Aged, Sensitivity and Specificity

Neurocognitive (NC) impairment (NCI) occurs commonly in people living with HIV. Despite substantial effort, no biomarkers have been sufficiently validated for diagnosis and prognosis of NCI in the clinic. The goal of this project was to identify diagnostic or prognostic biomarkers for NCI in a comprehensively characterized HIV cohort. Multidisciplinary case review selected 98 HIV-infected individuals and categorized them into four NC groups using normative data: stably normal (SN), stably impaired (SI), worsening (Wo), or improving (Im). All subjects underwent comprehensive NC testing, phlebotomy, and lumbar puncture at two timepoints separated by a median of 6.2 months. Eight biomarkers were measured in CSF and blood by immunoassay. Results were analyzed using mixed model linear regression and staged recursive partitioning. At the first visit, subjects were mostly middle-aged (median 45) white (58 %) men (84 %) who had AIDS (70 %). Of the 73 % who took antiretroviral therapy (ART), 54 % had HIV RNA levels below 50 c/mL in plasma. Mixed model linear regression identified that only MCP-1 in CSF was associated with neurocognitive change group. Recursive partitioning models aimed at diagnosis (i.e., correctly classifying neurocognitive status at the first visit) were complex and required most biomarkers to achieve misclassification limits. In contrast, prognostic models were more efficient. A combination of three biomarkers (sCD14, MCP-1, SDF-1α) correctly classified 82 % of Wo and SN subjects, including 88 % of SN subjects. A combination of two biomarkers (MCP-1, TNF-α) correctly classified 81 % of Im and SI subjects, including 100 % of SI subjects. This analysis of well-characterized individuals identified concise panels of biomarkers associated with NC change. Across all analyses, the two most frequently identified biomarkers were sCD14 and MCP-1, indicators of monocyte/macrophage activation. While the panels differed depending on the outcome and on the degree of misclassification, nearly all stable patients were correctly classified.

Alternate JournalJ Neuroimmune Pharmacol
PubMed ID24101401
PubMed Central IDPMC3874146
Grant ListHHSN271201000036C / / PHS HHS / United States
K24 MH097673 / MH / NIMH NIH HHS / United States
DRF-2010-03-97 / / Department of Health / United Kingdom
P30 MH62512 / MH / NIMH NIH HHS / United States
U24 MH100928 / MH / NIMH NIH HHS / United States
HHSN271201000036C / MH / NIMH NIH HHS / United States
S10 RR031646 / RR / NCRR NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
U01 MH083506 / MH / NIMH NIH HHS / United States