Michael J Peluso1, Victor Valcour2, Jintanat Ananworanich3, Pasiri Sithinamsuwan4, Thep Chalermchai5, James L K Fletcher5, Sukalya Lerdlum6, Nitiya Chomchey5, Bonnie Slike7, Napapon Sailasuta8, Magnus Gisslén9, Henrik Zetterberg10, Serena Spudich11. 1. Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. 2. Memory and Aging Center, Department of Neurology, University of California, San Francisco. 3. US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland SEARCH, The Thai Red Cross AIDS Research Center. 4. Division of Neurology, Department of Internal Medicine, Phramongkutklao Hospital. 5. SEARCH, The Thai Red Cross AIDS Research Center. 6. Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 7. US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland. 8. Huntington Medical Research Institutes, Pasadena, California. 9. Institute of Biomedicine, Department of Infectious Diseases, The Sahlgrenska Academy at the University of Gothenburg. 10. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden UCL Institute of Neurology, Queen Square, London, United Kingdom. 11. Department of Neurology, Yale University School of Medicine, New Haven, Connecticut.
Abstract
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.
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.
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