Effect of antiretroviral treatment on blood-brain barrier integrity in HIV-1 infection

BMC Neurology

Aylin Yilmaz¹  Birgitta Anesten¹  Magnus Gisslén¹  Bruce J. Brew²  Richard W. Price³  Henrik Zetterberg⁴  Dietmar Fuchs⁵  Staffan Nilsson⁶ 

[1] Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE-415 50, Gothenburg, Sweden;Department of Infectious Diseases, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden;Department of Neurology, St.Vincent’s Hospital, Sydney, NSW, Australia;Department of HIV Medicine and Peter Duncan Neurosciences Unit, St Vincent’s Centre for Applied Medical Research, St. Vincent’s Hospital, Sydney, NSW, Australia;Department of Neurology, University of California San Francisco, San Francisco, California, USA;Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden;Clinical Neurochemistry Laboratory Sahlgrenska University Hospital, Mölndal, Sweden;Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK;UK Dementia Research Institute at UCL, London, UK;Hong Kong Center for Neurodegenerative Disease, Hong Kong, China;Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria;Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden;

关键词: HIV;    Cerebrospinal fluid;    Blood-brain-barrier;    Albumin ratio;    Antiretroviral therapy;    Biomarkers;   

DOI  :  10.1186/s12883-021-02527-8

来源: Springer

【 摘 要 】

BackgroundBlood-brain barrier (BBB) injury is prevalent in patients with HIV-associated dementia (HAD) and is a frequent feature of HIV encephalitis. Signs of BBB damage are also sometimes found in neuroasymptomatic HIV-infected individuals without antiretroviral therapy (ART). The aim of this study was to investigate the integrity of the BBB before and after initiation of ART in both neuroasymptomatic HIV infection and in patients with HAD.MethodsWe determined BBB integrity by measuring cerebrospinal fluid (CSF)/plasma albumin ratios in archived CSF samples prior to and after initiation of ART in longitudinally-followed neuroasymptomatic HIV-1-infected individuals and patients with HAD. We also analyzed HIV RNA in blood and CSF, IgG Index, CSF WBC counts, and CSF concentrations of β2-micoglobulin, neopterin, and neurofilament light chain protein (NfL).ResultsWe included 159 HIV-infected participants; 82 neuroasymptomatic individuals and 77 with HAD. All neuroasymptomatic individuals (82/82), and 10/77 individuals with HAD, were longitudinally followed with a median (interquartile range, IQR) follow-up of 758 (230–1752) days for the neuroasymptomatic individuals, and a median (IQR) follow-up of 241 (50–994) days for the individuals with HAD. Twelve percent (10/82) of the neuroasymptomatic individuals and 80% (8/10) of the longitudinally-followed individuals with HAD had elevated albumin ratios at baseline. At the last follow-up, 9% (7/82) of the neuroasymptomatic individuals and 20% (2/10) of the individuals with HAD had elevated albumin ratios. ART significantly decreased albumin ratios in both neuroasymptomatic individuals and in patients with HAD.ConclusionThese findings indicate that ART improves and possibly normalizes BBB integrity in both neuroasymptomatic HIV-infected individuals and in patients with HAD.

【 授权许可】

CC BY