Primary HIV-1 infection is characterized by elevation of cerebrospinal fluid biomarkers indicating early neuronal damage

• Background The extent of neurologic damage during presymptomatic HIV-infection is incompletely understood. Cerebrospinal fluid (CSF) biomarkers such as neurofilament light chain (NFL) are elevated in subjects with advanced HIVinfection and HIV-associated dementia, and are associated with central nervous system impairment. We measured NFL and other CSF biomarkers of neuronal injury during primary HIVinfection (PHI). Methods In antiretroviral naïve subjects with PHI, CSF NFL was analyzed using a new, highly-sensitive, twosite enzymatic quantitative immunoassay with a lower limit of detection of 50 ng/L. Detection of t-tau, β-amyloid, and soluble amyloid precursor protein-alpha and -beta (sAPP-α and sAPP-β) used standard ELISAs. Analyses employed the Mann-Whitney test and Spearman correlations. Results 84 PHI subjects had a median age 36(18-61) years, CD4+ T cell count 546(111-1608) cells/uL, and log10 plasma HIV RNA level of 4.57(1.69-7.08) at 96.5(15-376) days post-infection. HIV-uninfected controls had a median age of 43(26-66) years. Median NFL in 81PHI subjects was elevated at 565(120-2830) ng/L, compared with 364(193-793) ng/L in 20 controls (p<0.01).Median sAPP-α was 721(293-1285) ng/L in 21 PHI subjects compared with 435(324-783) ng/L in 23 controls (p00.02). History of neurologically symptomatic seroconversion was not associated with higher NFL. No significant differences in t-tau, sAPP-β, and β-amyloid were detected between a subset of PHI subjects and controls. NFL correlated with CSF inflammatory markers including neopterin (r00.40; p00.0002), IP-10 (r00.42;p00.001), white blood cell count (r00.33; p00.003), and CSF:plasma albumin ratio (r00.59;p<0.0001). NFL also correlated with plasma (r00.23; p0 0.04) and CSF (r00.23;p00.04) HIV RNA levels, CSF t-tau (r00.51;p00.004) and CSF β-amyloid (r00.5; p00.02),. Conclusion Biomarkers of neuronal damage are elevated in subjects with PHI compared to HIVuninfected controls. NFL, a sensitive marker of neuronal injury, correlates with markers of CSF inflammation during PHI. These findings suggest that HIV-related neuronal damage starts during early HIV-infection and is mediated by neuroimmune activation during this period.

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MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

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