Absence of Cerebrospinal Fluid Signs of Neuronal Injury Before and After Immediate Antiretroviral Therapy in Acute HIV Infection

J Infect Dis. 2015 Dec 1;212(11):1759-67. doi: 10.1093/infdis/jiv296. Epub 2015 May 20.


Background: It is unknown whether neuronal injury begins during acute human immunodeficiency virus (HIV) infection, and whether immediate initiation of combination antiretroviral therapy (cART) prevents neuronal injury.

Methods: Cerebrospinal fluid (CSF) neurofilament light chain (NFL), a measure of axonal injury, was assessed before and after cART initiation in individuals starting treatment during acute or chronic HIV infection. Nonparametric statistics examined relationships between NFL and disease progression, neuroinflammation, and cognitive performance.

Results: Before treatment, subjects with acute infection had lower CSF NFL levels, with elevations for their age in 1 of 32 subjects with acute infection (3.1%) and 10 of 32 with chronic infection (31%) (P = .006). This persisted after cART initiation, with 1 of 25 acute (4%) and 4 of 9 chronic subjects (44%) showing elevated NFL levels (P = .01). In acute infection, pre-cART NFL levels were inversely correlated with proton magnetic resonance spectroscopic findings of N-acetylaspartate/creatine in frontal gray matter (r = -0.40; P = .03), frontal white matter (r = -0.46; P = .01), and parietal gray matter (r = -0.47; P = .01); correlations persisted after treatment in the frontal white matter (r = -0.51; P = .02) and parietal gray matter (r = -0.46; P = .04).

Conclusions: CSF NFL levels are not elevated in untreated acute HIV infection or after 6 months of immediately initiated cART but are abnormal in chronic HIV infection before and after treatment. In acute HIV infection, CSF NFL levels are inversely associated with neuroimaging markers of neuronal health.

Keywords: HIV/AIDS; antiretroviral therapy; magnetic resonance spectroscopy; neurofilament light chain; neuroinflammation; neurological injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Anti-Retroviral Agents* / administration & dosage
  • Anti-Retroviral Agents* / therapeutic use
  • Cohort Studies
  • Female
  • HIV Infections / cerebrospinal fluid*
  • HIV Infections / drug therapy*
  • HIV Infections / epidemiology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neurofilament Proteins / cerebrospinal fluid*
  • Neuroimaging
  • Young Adult


  • Anti-Retroviral Agents
  • Neurofilament Proteins