Blood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy. (29th March 2017)

• Record Type: Journal Article
• Authors: Rahimy, Elham; Li, Fang-Yong; Hagberg, Lars; Fuchs, Dietmar; Robertson, Kevin; Meyerhoff, Dieter J.; Zetterberg, Henrik; Price, Richard W.; Gisslén, Magnus; Spudich, Serena
• Is Part Of: Journal of infectious diseases. Volume 215:Number 7(2017:Apr. 01)
• Page Start: 1132
• Page End: 1140
• Publication Date: 2017-03-29
• Subjects: HIV/AIDS -- PHI -- primary HIV infection -- BBB -- Blood brain barrier -- neuropathogenesis.; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jix013
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: 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.