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Blood–Brain Barrier Impairment in Patients Living with HIV: Predictors and Associated Biomarkers

Despite the substantial changes resulting from the introduction of combination antiretroviral therapy (cART), the prevalence of HIV-associated neurocognitive disorders (HAND) remains substantial. Blood–brain barrier impairment (BBBi) is a frequent feature in people living with HIV (PLWH) and it may...

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Autores principales: Caligaris, Giulia, Trunfio, Mattia, Ghisetti, Valeria, Cusato, Jessica, Nigra, Marco, Atzori, Cristiana, Imperiale, Daniele, Bonora, Stefano, Di Perri, Giovanni, Calcagno, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151579/
https://www.ncbi.nlm.nih.gov/pubmed/34065785
http://dx.doi.org/10.3390/diagnostics11050867
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author Caligaris, Giulia
Trunfio, Mattia
Ghisetti, Valeria
Cusato, Jessica
Nigra, Marco
Atzori, Cristiana
Imperiale, Daniele
Bonora, Stefano
Di Perri, Giovanni
Calcagno, Andrea
author_facet Caligaris, Giulia
Trunfio, Mattia
Ghisetti, Valeria
Cusato, Jessica
Nigra, Marco
Atzori, Cristiana
Imperiale, Daniele
Bonora, Stefano
Di Perri, Giovanni
Calcagno, Andrea
author_sort Caligaris, Giulia
collection PubMed
description Despite the substantial changes resulting from the introduction of combination antiretroviral therapy (cART), the prevalence of HIV-associated neurocognitive disorders (HAND) remains substantial. Blood–brain barrier impairment (BBBi) is a frequent feature in people living with HIV (PLWH) and it may persist despite effective antiretroviral treatment. A cross-sectional study was performed in PLWH who underwent lumbar puncture for clinical reasons or research protocols and several cerebrospinal fluid biomarkers were studied. BBBi was defined as cerebrospinal fluid-to-serum albumin ratio (CSAR) >6.5 (<40 years) or >8 (>40 years). We included 464 participants: 147 cART-naïve and 317 on cART. Male sex was prevalent in both groups (72.1% and 72.2% respectively); median age was 44 (38–52) years in naïve and 49 (43–57) years in treated subjects. BBBi was observed in 35.4% naïve and in 22.7% treated participants; the use of integrase inhibitors was associated with a lower prevalence (18.3 vs. 30.9%, p = 0.050). At multivariate binary logistic regression (including age and sex) nadir CD4 cell count (p = 0.034), presence of central nervous system (CNS) opportunistic infections (p = 0.024) and cerebrospinal fluid (CSF) HIV RNA (p = 0.002) in naïve participants and male sex (p = 0.021), a history of CNS opportunistic infections (p = 0.001) and CSF HIV RNA (p = 0.034) in treated patients were independently associated with BBBi. CSF cells and neopterin were significantly higher in participants with BBBi. BBBi was prevalent in naïve and treated PLWH and it was associated with CSF HIV RNA and neopterin. Systemic control of viral replication seems to be essential for BBB integrity while sex and treatment influence need further studies.
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spelling pubmed-81515792021-05-27 Blood–Brain Barrier Impairment in Patients Living with HIV: Predictors and Associated Biomarkers Caligaris, Giulia Trunfio, Mattia Ghisetti, Valeria Cusato, Jessica Nigra, Marco Atzori, Cristiana Imperiale, Daniele Bonora, Stefano Di Perri, Giovanni Calcagno, Andrea Diagnostics (Basel) Article Despite the substantial changes resulting from the introduction of combination antiretroviral therapy (cART), the prevalence of HIV-associated neurocognitive disorders (HAND) remains substantial. Blood–brain barrier impairment (BBBi) is a frequent feature in people living with HIV (PLWH) and it may persist despite effective antiretroviral treatment. A cross-sectional study was performed in PLWH who underwent lumbar puncture for clinical reasons or research protocols and several cerebrospinal fluid biomarkers were studied. BBBi was defined as cerebrospinal fluid-to-serum albumin ratio (CSAR) >6.5 (<40 years) or >8 (>40 years). We included 464 participants: 147 cART-naïve and 317 on cART. Male sex was prevalent in both groups (72.1% and 72.2% respectively); median age was 44 (38–52) years in naïve and 49 (43–57) years in treated subjects. BBBi was observed in 35.4% naïve and in 22.7% treated participants; the use of integrase inhibitors was associated with a lower prevalence (18.3 vs. 30.9%, p = 0.050). At multivariate binary logistic regression (including age and sex) nadir CD4 cell count (p = 0.034), presence of central nervous system (CNS) opportunistic infections (p = 0.024) and cerebrospinal fluid (CSF) HIV RNA (p = 0.002) in naïve participants and male sex (p = 0.021), a history of CNS opportunistic infections (p = 0.001) and CSF HIV RNA (p = 0.034) in treated patients were independently associated with BBBi. CSF cells and neopterin were significantly higher in participants with BBBi. BBBi was prevalent in naïve and treated PLWH and it was associated with CSF HIV RNA and neopterin. Systemic control of viral replication seems to be essential for BBB integrity while sex and treatment influence need further studies. MDPI 2021-05-12 /pmc/articles/PMC8151579/ /pubmed/34065785 http://dx.doi.org/10.3390/diagnostics11050867 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Caligaris, Giulia
Trunfio, Mattia
Ghisetti, Valeria
Cusato, Jessica
Nigra, Marco
Atzori, Cristiana
Imperiale, Daniele
Bonora, Stefano
Di Perri, Giovanni
Calcagno, Andrea
Blood–Brain Barrier Impairment in Patients Living with HIV: Predictors and Associated Biomarkers
title Blood–Brain Barrier Impairment in Patients Living with HIV: Predictors and Associated Biomarkers
title_full Blood–Brain Barrier Impairment in Patients Living with HIV: Predictors and Associated Biomarkers
title_fullStr Blood–Brain Barrier Impairment in Patients Living with HIV: Predictors and Associated Biomarkers
title_full_unstemmed Blood–Brain Barrier Impairment in Patients Living with HIV: Predictors and Associated Biomarkers
title_short Blood–Brain Barrier Impairment in Patients Living with HIV: Predictors and Associated Biomarkers
title_sort blood–brain barrier impairment in patients living with hiv: predictors and associated biomarkers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151579/
https://www.ncbi.nlm.nih.gov/pubmed/34065785
http://dx.doi.org/10.3390/diagnostics11050867
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