A concise panel of biomarkers diagnoses and predicts neurocognitive (NC) status in HIV-Infected individuals.

Type: Published Abstract
Title: A concise panel of biomarkers diagnoses and predicts neurocognitive (NC) status in HIV-Infected individuals.
Authors: Letendre S, Marcotte T, Deutsch R, Franklin D, Rosario D, Alexander T, Haughey N, Pardo C, Fox H, Grant I
Year: 2012
Publication: 19th Conference on Retroviruses and Opportunistic Infections
Volume: Issue: Pages:
Abstract:Background: 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 NIMH AIDS Research Centers are performing hypothesis- and discovery-driven analyses to address this unmet need. Methods: Case conference review categorized 99 HIV-infected individuals into one of four groups using objectively determined norms: stably normal (SN), stably impaired (SI), reliably worsening (RW), or reliably improving (RI). All subjects underwent comprehensive NC testing, phlebotomy, and lumbar puncture at two timepoints (T1 & T2) separated by a median of 6.3 months (IQR 5.6-70). A third visit was also reviewed to confirm group assignment. CCL2, CXCL10, CX3CL1, CXCL12, IL-6, TNF-α, soluble TNF receptors (sTNFR, p75), and sCD14 were measured in both fluids by immunoassay. Results were analyzed using recursive partitioning in two stages: We first identified biomarkers having a minimum number of nodes (decision points) with a ≤ 10% misclassification rate and then re-analyzed the data to allow up to 20% misclassification. Results: At T1, subjects were mostly middle-aged (median 45) white (58%) men (84%) who had AIDS (70%). Among those taking ART (74%), most had HIV RNA levels below 50 c/mL in plasma (54%) and CSF (85%) and had immune recovery (median CD4+ cell counts: nadir 110, current 394). A combination of 5 biomarkers (sCD14, CCL2, CXCL10, sTNFR, TNF-α) correctly diagnosed NC status at T1 in 92%. Allowing 20% misclassification eliminated 1 biomarker (TNF-α). Among subjects with normal performance at T1, a combination of 5 biomarkers (sCD14, IL-6, CXCL12, CCL2, sTNFR) correctly classified T2 status in 94%. Three of these (sCD14, CXCL12, IL-6) correctly classified 82%, including 100% of subjects in the SN group. Among subjects with impaired performance at T1, 4 biomarkers (CCL2, TNF-α, sCD14, CX3CL1) correctly classified 96%. Two of these (CCL2, TNF-α) correctly classified 81%, including 100% of subjects in the SI group. Conclusions: This analysis of well-characterized individuals identified concise panels of diagnostic and prognostic biomarkers for NCI. The two most frequently identified biomarkers were sCD14 and CCL2, indicators of monocyte/macrophage activation. While the panels differed depending on the outcome and on the degree of misclassification, all cases of NC stability were correctly classified.