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However, despite efficient therapy, milder forms of neurocognitive symptoms are still present in people living with HIV. Plasma homocysteine is a marker of vitamin B deficiency and has been associated with cognitive impairment. People living with HIV have higher homocysteine concentrations than HIV-negative controls, and we have previously found an association between plasma homocysteine concentration and CSF concentration of neurofilament light protein, a sensitive marker for ongoing neuronal injury in HIV. This prompted us to perform this randomized controlled trial, to evaluate the effect of vitamin B supplementation on neuronal injury in a cohort of people living with HIV on stable antiretroviral therapy. At the Department of Infectious Diseases at Sahlgrenska University Hospital in Gothenburg, Sweden, 124 virally suppressed people living with HIV were screened to determine eligibility for this study. Sixty-one fulfilled the inclusion criteria by having plasma homocysteine levels at or above 12\u2005\u03bcmol\/l. They were randomized (1:1) to either active treatment (with cyanocobalamin 0.5\u2005mg, folic acid 0.8\u2005mg and pyridoxine 3.0\u2005mg) q.d. or to a control arm with a cross over to active treatment after 12 months. Cognitive function was measured repeatedly during the trial, which ran for 24 months. We found a significant correlation between plasma neurofilament light protein and plasma homocysteine at screening (n = 124, r = 0.35, P &amp;lt; 0.0001). Plasma homocysteine levels decreased by 35% from a geometric mean of 15.7\u2005\u03bcmol\/l (95% confidence interval 14.7\u201316.7) to 10.3\u2005\u03bcmol\/l (95% confidence interval 9.3\u201311.3) in the active treatment arm between baseline and Month 12. No significant change was detected in the control arm during the same time period [geometric mean 15.2 (95% confidence interval 14.3\u201316.2) versus geometric mean 16.5\u2005\u03bcmol\/l (95% confidence interval 14.7\u201318.6)]. A significant difference in change in plasma homocysteine levels was seen between arms at 12 months [\u221240% (95% confidence interval \u221248 to \u221230%), P &amp;lt; 0.001]. However, no difference between arms was seen in either plasma neurofilament light protein levels [\u22126.5% (\u221220 to 9%), P = 0.39], or cognitive measures [\u22120.08 (\u22120.33 to 0.17), P = 0.53]. Our results do not support a vitamin B\u2013dependent cause of the correlation between neurofilament light protein and homocysteine. Additional studies are needed to further elucidate this matter.<\/jats:p>","DOI":"10.1093\/braincomms\/fcac259","type":"journal-article","created":{"date-parts":[[2022,10,15]],"date-time":"2022-10-15T12:10:57Z","timestamp":1665835857000},"source":"Crossref","is-referenced-by-count":3,"title":["The effect of vitamin B supplementation on neuronal injury in people living with HIV: a randomized controlled trial"],"prefix":"10.1093","volume":"4","author":[{"given":"Erika","family":"Tyrberg","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg , Gothenburg , Sweden"},{"name":"Department of Infectious Diseases, Sahlgrenska University Hospital , Gothenburg , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Hagberg","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg , Gothenburg , Sweden"},{"name":"Department of Infectious Diseases, Sahlgrenska University Hospital , Gothenburg , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars-Magnus","family":"Andersson","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg , Gothenburg , Sweden"},{"name":"Department of Infectious Diseases, Sahlgrenska University Hospital , Gothenburg , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Staffan","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Department of Mathematical Sciences, Chalmers University of Technology , Gothenburg , Sweden"},{"name":"Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg , Gothenburg , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aylin","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg , Gothenburg , Sweden"},{"name":"Department of Infectious Diseases, Sahlgrenska University Hospital , Gothenburg , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c5sa","family":"Mellgren","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg , Gothenburg , Sweden"},{"name":"Department of Infectious Diseases, Sahlgrenska University Hospital , Gothenburg , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg , M\u00f6lndal , Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , M\u00f6lndal , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg , M\u00f6lndal , Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , M\u00f6lndal , Sweden"},{"name":"Department of Neurodegenerative Disease, UCL Institute of Neurology , Queen Square, London , UK"},{"name":"UK Dementia Research Institute at UCL , London , UK"},{"name":"Hong Kong Center for Neurodegenerative Diseases , Hong Kong , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Gissl\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg , Gothenburg , Sweden"},{"name":"Department of Infectious Diseases, Sahlgrenska University Hospital , Gothenburg , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,10,15]]},"reference":[{"issue":"6","key":"2022110311574200700_fcac259-B1","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1002\/ana.410190602","article-title":"The AIDS dementia complex: I. 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