Effect of antiretroviral treatment on blood-brain barrier integrity in HIV-1 infection
Abstract Background Blood-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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-12-01
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| Series: | BMC Neurology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12883-021-02527-8 |
| _version_ | 1819102980912185344 |
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| author | Birgitta Anesten Henrik Zetterberg Staffan Nilsson Bruce J. Brew Dietmar Fuchs Richard W. Price Magnus Gisslén Aylin Yilmaz |
| author_facet | Birgitta Anesten Henrik Zetterberg Staffan Nilsson Bruce J. Brew Dietmar Fuchs Richard W. Price Magnus Gisslén Aylin Yilmaz |
| author_sort | Birgitta Anesten |
| collection | DOAJ |
| description | Abstract Background Blood-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. Methods We 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). Results We 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. Conclusion These findings indicate that ART improves and possibly normalizes BBB integrity in both neuroasymptomatic HIV-infected individuals and in patients with HAD. |
| first_indexed | 2024-12-22T01:43:11Z |
| format | Article |
| id | doaj.art-9eac7f7027464308ba73d195f4f04f91 |
| institution | Directory Open Access Journal |
| issn | 1471-2377 |
| language | English |
| last_indexed | 2024-12-22T01:43:11Z |
| publishDate | 2021-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neurology |
| spelling | doaj.art-9eac7f7027464308ba73d195f4f04f912022-12-21T18:43:09ZengBMCBMC Neurology1471-23772021-12-012111910.1186/s12883-021-02527-8Effect of antiretroviral treatment on blood-brain barrier integrity in HIV-1 infectionBirgitta Anesten0Henrik Zetterberg1Staffan Nilsson2Bruce J. Brew3Dietmar Fuchs4Richard W. Price5Magnus Gisslén6Aylin Yilmaz7Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of GothenburgDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgMathematical Sciences, Chalmers University of TechnologyDepartment of Neurology, St.Vincent’s HospitalDivision of Biological Chemistry, Biocenter, Innsbruck Medical UniversityDepartment of Neurology, University of California San FranciscoDepartment of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of GothenburgDepartment of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of GothenburgAbstract Background Blood-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. Methods We 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). Results We 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. Conclusion These findings indicate that ART improves and possibly normalizes BBB integrity in both neuroasymptomatic HIV-infected individuals and in patients with HAD.https://doi.org/10.1186/s12883-021-02527-8HIVCerebrospinal fluidBlood-brain-barrierAlbumin ratioAntiretroviral therapyBiomarkers |
| spellingShingle | Birgitta Anesten Henrik Zetterberg Staffan Nilsson Bruce J. Brew Dietmar Fuchs Richard W. Price Magnus Gisslén Aylin Yilmaz Effect of antiretroviral treatment on blood-brain barrier integrity in HIV-1 infection BMC Neurology HIV Cerebrospinal fluid Blood-brain-barrier Albumin ratio Antiretroviral therapy Biomarkers |
| title | Effect of antiretroviral treatment on blood-brain barrier integrity in HIV-1 infection |
| title_full | Effect of antiretroviral treatment on blood-brain barrier integrity in HIV-1 infection |
| title_fullStr | Effect of antiretroviral treatment on blood-brain barrier integrity in HIV-1 infection |
| title_full_unstemmed | Effect of antiretroviral treatment on blood-brain barrier integrity in HIV-1 infection |
| title_short | Effect of antiretroviral treatment on blood-brain barrier integrity in HIV-1 infection |
| title_sort | effect of antiretroviral treatment on blood brain barrier integrity in hiv 1 infection |
| topic | HIV Cerebrospinal fluid Blood-brain-barrier Albumin ratio Antiretroviral therapy Biomarkers |
| url | https://doi.org/10.1186/s12883-021-02527-8 |
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