Background
Neurofilament light chain (NFL) is a sensitive neuronal injury marker, with levels elevated in both neuroinflammatory and neurodegenerative diseases. Cerebrospinal fluid (CSF) NFL is elevated in up to 40% of people with HIV during the 1st year of infection and has been reported as normalizing after antiretroviral therapy (ART). We measured CSF NFL cross-sectionally during acute HIV infection (AHI) and at longitudinal time points up to 5 years after immediate initiation of ART in an observational study.
Methods
RV254 AHI cohort participants completed optional lumbar punctures during pre-ART AHI (week 0, n=136) and at post-ART visits (weeks 24, 48, 96 & 240, n=201). All post-ART sample donors had plasma HIV RNA ≤50 cps/ml. RV254 participant CSF NFL measurements were compared to 44 people without HIV (PWoH), both adjusted to an age of 30 (see footnotes in Figure), and also to age-based upper normal limits (UNL) based on published data. Chi-square test or non-parametric tests were used for statistical analysis.
Results
Among the 136 week 0 CSF samples, 135 (99%) were from males, with median age of 27 (IQR 23-32) years. The median plasma and CSF HIV RNA were 5.99 (IQR 5.08-6.78) and 3.22 (IQR 1.91-4.24) log10 cps/ml; median CD4+ T-cell counts were 379 (IQR 263-543) cells/mm3. At pre-ART week 0, RV254 participants had higher CSF NFL levels than PWoH (p<0.001, see Figure), and also had a higher rate of abnormal CSF NFL (>age-based UNL) than PWoH (20 (15%) vs. 1 (2%), p=0.029). Among AHI at week 0, CSF NFL positively correlated with CSF HIV RNA (r=0.206, p=0.016), CD8+ T-cell (r=0.249, p=0.004) and negatively correlated with CD4/CD8 ratio (r=-0.242, p=0.005).
During post-ART visits (ART initiation 20 (IQR 15-26) days of estimated infection), AHI CSF samples consistently showed higher NFL levels than controls (p<0.001), with 5/62 (8%) and 10/139 (7%) samples from week 24 and week 48 or later exceeding the age-based UNL. Only one CSF sample at week 24 and one at week 240 with abnormal NFL had detectable HIV RNA (316 & 20 cps/ml, respectively).
Conclusions
CSF samples collected cross-sectionally from pre-ART AHI and post-immediate ART time intervals in RV254 participants exhibited higher NFL levels than PWoH. Abnormal NFL levels were present in 7% of CSF samples collected at week 48 or later, most without detectable HIV RNA, suggesting ongoing neuronal injury in the absence of CSF viral escape. The clinical significance of this finding requires assessment of long-term outcomes in this group.
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