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

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Birgitta Anesten ◽  
Henrik Zetterberg ◽  
Staffan Nilsson ◽  
Bruce J. Brew ◽  
Dietmar Fuchs ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Hiv Encephalitis ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Hiv Rna ◽  
Blood Brain ◽  
Before And After ◽  
Hiv 1

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.

scholarly journals Extracellular vesicles of the blood-brain barrier: Role in the HIV-1 associated amyloid beta pathology

2017 ◽  
Vol 79 ◽  
pp. 12-22 ◽  
Author(s):  
Ibolya E. András ◽  
Ana Leda ◽  
Marta Garcia Contreras ◽  
Luc Bertrand ◽  
Minseon Park ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Extracellular Vesicles ◽  
Amyloid Beta ◽  
Brain Barrier ◽  
Blood Brain ◽  
Hiv 1

Tight Junction Regulation by Morphine and HIV-1 Tat Modulates Blood–Brain Barrier Permeability

2008 ◽  
Vol 28 (5) ◽  
pp. 528-541 ◽  
Author(s):  
Supriya D. Mahajan ◽  
Ravikumar Aalinkeel ◽  
Donald E. Sykes ◽  
Jessica L. Reynolds ◽  
B. Bindukumar ◽  
...  
Keyword(s):  
Tight Junction ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
Tight Junction Regulation ◽  
Hiv 1

scholarly journals HIV-1 Tat and opioids act independently to limit antiretroviral brain concentrations and reduce blood–brain barrier integrity

2019 ◽  
Vol 25 (4) ◽  
pp. 560-577 ◽  
Author(s):  
Crystal R. Leibrand ◽  
Jason J. Paris ◽  
Austin M. Jones ◽  
Quamrun N. Masuda ◽  
Matthew S. Halquist ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Hiv 1 ◽  
Blood Brain Barrier Integrity

HIV-1 protein gp120 crosses the blood-brain barrier: Role of adsorptive endocytosis

Life Sciences ◽  
1997 ◽  
Vol 61 (9) ◽  
pp. PL119-PL125 ◽  
Author(s):  
William A. Banks ◽  
Abba J. Kastin ◽  
Victoria Akerstrom
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Protein Gp120 ◽  
Blood Brain ◽  
Adsorptive Endocytosis ◽  
Hiv 1

scholarly journals GRL-04810 and GRL-05010, Difluoride-Containing Nonpeptidic HIV-1 Protease Inhibitors (PIs) That Inhibit the Replication of Multi-PI-Resistant HIV-1In Vitroand Possess Favorable Lipophilicity That May Allow Blood-Brain Barrier Penetration

2013 ◽  
Vol 57 (12) ◽  
pp. 6110-6121 ◽  
Author(s):  
Pedro Miguel Salcedo Gómez ◽  
Masayuki Amano ◽  
Sofiya Yashchuk ◽  
Akira Mizuno ◽  
Debananda Das ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
Blood Brain Barrier ◽  
Wide Spectrum ◽  
Laboratory Strain ◽  
Cyclic Ether ◽  
Brain Barrier ◽  
Blood Brain ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACTWe designed, synthesized, and identified two novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs), GRL-04810 and GRL-05010, containing the structure-based designed privileged cyclic ether-derived nonpeptide P2 ligand,bis-tetrahydrofuranylurethane (bis-THF), and a difluoride moiety, both of which are active against the laboratory strain HIV-1LAI(50% effective concentrations [EC50s], 0.0008 and 0.003 μM, respectively) with minimal cytotoxicity (50% cytotoxic concentrations [CC50s], 17.5 and 37.0 μM, respectively, in CD4+MT-2 cells). The two compounds were active against multi-PI-resistant clinical HIV-1 variants isolated from patients who had no response to various antiviral regimens. GRL-04810 and GRL-05010 also blocked the infectivity and replication of each of the HIV-1NL4-3variants selected by up to 5 μM lopinavir (EC50s, 0.03 and 0.03 μM, respectively) and atazanavir (EC50s, 0.02 and 0.04 μM, respectively). Moreover, they were active against darunavir (DRV)-resistant variants (EC50in 0.03 to 0.034 μM range for GRL-04810 and 0.026 to 0.043 μM for GRL-05010), while DRV had EC50s between 0.02 and 0.174 μM. GRL-04810 had a favorable lipophilicity profile as determined with the partition (logP) and distribution (logD) coefficients of −0.14 and −0.29, respectively. Thein vitroblood-brain barrier (BBB) permeability assay revealed that GRL-04810 and GRL-05010 may have a greater advantage in terms of crossing the BBB than the currently available PIs, with apparent penetration indexes of 47.8 × 10−6and 61.8 × 10−6cm/s, respectively. The present data demonstrate that GRL-04810 and GRL-05010 exert efficient activity against a wide spectrum of HIV-1 variantsin vitroand suggest that two fluorine atoms added to theirbis-THF moieties may well enhance their penetration across the BBB.

scholarly journals Tumour necrosis factor-α mediates blood—brain barrier damage in HIV-1 infection of the central nervous system

1992 ◽  
Vol 1 (3) ◽  
pp. 191-196 ◽  
Author(s):  
M. K. Sharief ◽  
M. Ciardi ◽  
E. J. Thompson ◽  
F. Sorice ◽  
F. Rossi ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Tumour Necrosis ◽  
Brain Barrier ◽  
Tumour Necrosis Factor Α ◽  
Blood Brain ◽  
Tnf Α ◽  
Factor Α ◽  
Hiv 1 ◽  
Blood Brain Barrier Damage ◽  
Necrosis Factor

The pathogenesis of brain inflammation and damage by human immunodeficiency virus (HIV) infection is unclear. Because blood–brain barrier damage and impaired cerebral perfusion are common features of HIV-1 infection, we evaluated the role of tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in mediating disruption of the blood–brain barrier. Levels of TNF-α were more elevated in cerebrospinal fluid (CSF) than in serum of HIV-1 infected patients and were mainly detected in those patients who had neurologic involvement. Intrathecal TNF-α levels correlated with signs of blood–brain barrier damage, manifested by high CSF to serum albumin quotient, and with the degree of barrier impairment. In contrast, intrathecal IL-1β levels did not correlate with blood-brain barrier damage in HIV-1 infected patients. TNF-α seems to be related to active neural inflammation and to blood–brain barrier damage. The proinflammatory effects of TNF-α in the nervous system are dissociated from those of IL-1β.

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