The character of central nervous system (CNS)
HIV infection and its effects on neuronal integrity vary with evolving systemic
infection. Using a cross-sectional design and archived samples, we compared concentrations of cerebrospinal fluid (CSF) neuronal
biomarkers in 143 samples from 8 HIV-infected subject groups representing a spectrum of untreated systemic HIV progression and viral suppression: primary
infection; four groups of chronic
HIV infection neuroasymptomatic (NA) subjects defined by blood CD4+ T cells of >350, 200-349, 50-199, and <50 cells/µL; HAD; treatment-induced viral suppression; and 'elite' controllers. Samples from 20 HIV-uninfected controls were also examined. The neuronal
biomarkers included neurofilament light chain
protein (NFL), total and phosphorylated tau (t-tau, p-tau), soluble
amyloid precursor
proteins alpha and beta (sAPPα, sAPPβ) and
amyloid beta (Aβ) fragments 1-42, 1-40 and 1-38. Comparison of the
biomarker changes showed a hierarchy of sensitivity in detection and suggested evolving mechanisms with progressive injury. NFL was the most sensitive neuronal
biomarker. Its CSF concentration exceeded age-adjusted norms in all HAD patients, 75% of NA CD4<50, 40% of NA CD4 50-199, and 42% of primary
infection, indicating common neuronal injury with untreated systemic HIV
disease progression as well as transiently during early
infection. By contrast, only 75% of HAD subjects had abnormal CSF t-tau levels, and there were no significant differences in t-tau levels among the remaining groups. sAPPα and β were also abnormal (decreased) in HAD, showed less marked change than NFL with CD4 decline in the absence of HAD, and were not decreased in PHI. The CSF Aβ
peptides and p-tau concentrations did not differ among the groups, distinguishing the HIV CNS injury profile from
Alzheimer's disease. These CSF
biomarkers can serve as useful tools in selected research and clinical settings for patient classification, pathogenetic analysis, diagnosis and management.