Blood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy

J Infect Dis. 2017 Apr 1;215(7):1132-1140. doi: 10.1093/infdis/jix013.


Background: We explored the establishment of abnormal blood-brain barrier (BBB) permeability and its relationship to neuropathogenesis during primary human immunodeficiency virus (HIV) infection by evaluating the cerebrospinal fluid (CSF) to serum albumin quotient (QAlb) in patients with primary HIV infection. We also analyzed effects of initiating combination antiretroviral therapy (cART).

Methods: The QAlb was measured in longitudinal observational studies of primary HIV infection. We analyzed trajectories of the QAlb before and after cART initiation, using mixed-effects models, and associations between the QAlb and the CSF level of neurofilament light chain (NFL), the ratio of N-acetylaspartate to creatinine levels (a magnetic resonance spectroscopy neuronal integrity biomarker), and neuropsychological performance.

Results: The baseline age-adjusted QAlb was elevated in 106 patients with primary HIV infection (median time of measurement, 91 days after infection), compared with that in 64 controls (P = .02). Before cART initiation, the QAlb increased over time in 84 participants with a normal baseline QAlb (P = .006) and decreased in 22 with a high baseline QAlb (P = .011). The QAlb did not change after a median cART duration of 398 days, initiated at a median interval of 225 days after infection (P = .174). The QAlb correlated with the NFL level at baseline (r = 0.497 and P < .001) and longitudinally (r = 0.555 and P < .001) and with the ratio of N-acetylaspartate to creatinine levels in parietal gray matter (r = -0.352 and P < .001 at baseline and r = -0.387 and P = .008 longitudinally) but not with neuropsychological performance.

Conclusion: The QAlb rises during primary HIV infection, associates with neuronal injury, and does not significantly improve over a year of treatment. BBB-associated neuropathogenesis in HIV-infected patients may initiate during primary infection.

Keywords: BBB; Blood brain barrier; HIV/AIDS; PHI; neuropathogenesis.; primary HIV infection.

Publication types

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

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active*
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid
  • Blood-Brain Barrier / diagnostic imaging
  • Blood-Brain Barrier / physiopathology*
  • Creatinine / cerebrospinal fluid
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy*
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neurofilament Proteins / cerebrospinal fluid
  • Prospective Studies
  • Viral Load


  • Biomarkers
  • Neurofilament Proteins
  • Aspartic Acid
  • N-acetylaspartate
  • Creatinine