Cerebrospinal fluid and neuroimaging biomarker abnormalities suggest early neurological injury in a subset of individuals during primary HIV infection

Abstract

Background: Cerebrospinal fluid (CSF) and neuroimaging abnormalities demonstrate neuronal injury during chronic AIDS, but data on these biomarkers during primary human immunodeficiency virus (HIV) infection is limited.

Methods: We compared CSF concentrations of neurofilament light chain, t-tau, p-tau, amyloid precursor proteins, and amyloid-beta 42 in 92 subjects with primary HIV infection and 25 controls. We examined relationships with disease progression and neuroinflammation, neuropsychological testing, and proton-magnetic resonance spectroscopy (MRS)-based metabolites.

Results: Neurofilament light chain was elevated in primary HIV infection compared with controls (P = .0004) and correlated with CSF neopterin (r = 0.38; P = .0005), interferon gamma-induced protein 10 (r = 0.39; P = .002), white blood cells (r = 0.32; P = .004), protein (r = 0.59; P < .0001), and CSF/plasma albumin ratio (r = 0.60; P < .0001). Neurofilament light chain correlated with decreased N-acteylaspartate/creatine and glutamate/creatine in the anterior cingulate (r = -0.35, P = .02; r = -0.40, P = .009, respectively), frontal white matter (r = -0.43, P = .003; r = -0.30, P = .048, respectively), and parietal gray matter (r = -0.43, P = .003; r = -0.47, P = .001, respectively). Beta-amyloid was elevated in the primary infection group (P = .0005) and correlated with time infected (r = 0.34; P = .003). Neither marker correlated with neuropsychological abnormalities. T-tau and soluble amyloid precursor proteins did not differ between groups.

Conclusions: Elevated neurofilament light chain and its correlation with MRS-based metabolites suggest early neuronal injury in a subset of participants with primary HIV infection through mechanisms involving central nervous system inflammation.

Figure 1.

A–F, Cerebrospinal fluid biomarkers of neuronal injury in the primary human immunodeficiency virus (HIV) infection group and HIV-uninfected control group. Abbreviations: CSF, cerebrospinal fluid; HIV-, human immunodeficiency virus–uninfected control group; NFL, neurofilament light chain; PHI, primary human immunodeficiency virus infection group; p-tau, hyperphosphorylated tau; sAPP, soluble amyloid precursor protein; t-tau, total tau.

Figure 2.

A–H, Correlates of neurofilament light chain levels in primary human immunodeficiency virus infection. r represents the Spearman correlation coefficient and corresponding P value. Solid lines represent best-fit regression line, and dashed lines represent 95% confidence intervals. Abbreviations: CSF, cerebrospinal fluid; IP-10, interferon gamma-induced protein 10; NFL, neurofilament light chain; WBC, white blood cell.

Figure 3.

A–H, Correlations of neurofilament light chain levels with regional proton-magnetic resonance spectroscopy–derived metabolite ratios. r represents the Spearman correlation coefficient and corresponding P value. Solid lines represent best-fit regression line, and dashed lines represent 95% confidence intervals. Abbreviations: Glu/Cr, glutamate/creatine; NAA/Cr, N-acetylaspartate/creatine; NFL, neurofilament light chain.

Figure 4.

A–G, Correlates of beta-amyloid in primary human immunodeficiency virus infection. Solid lines represent best-fit regression line, and dashed lines represent 95% confidence intervals. Abbreviations: CSF, cerebrospinal fluid; NFL, neurofilament light chain; sAPP, soluble amyloid precursor protein.