Association between tight junction proteins and cognitive performance in untreated Persons living with HIV (PLWH)

Francesca Bai; Valeria Bono; Lidia Borghi; Federica Bonazza; Camilla Falcinella; Virginia Vitaletti; Federica Miraglia; Mattia Trunfio; Andrea Calcagno; Jessica Cusato; Elena Vegni; Antonella D'arminio Monforte; Giulia Marchetti

doi:10.1097/QAD.0000000000003923

Association between tight junction proteins and cognitive performance in untreated Persons living with HIV (PLWH)

AIDS. 2024 May 3. doi: 10.1097/QAD.0000000000003923. Online ahead of print.

Affiliations

¹ Clinic of Infectious Diseases, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy.
² Unit of Clinical Psychology, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy.
³ Clinic of Infectious Diseases, Amedeo di Savoia Hospital, Department of Medical Sciences, University of Turin.
⁴ Laboratory of Pharmacology and Pharmacotherapy, Amedeo di Savoia Hospital, Department of Medical Sciences, University of Turin.

PMID: 38704619
DOI: 10.1097/QAD.0000000000003923

Abstract

Background: HIV-associated neurocognitive disorders (HAND) still affects persons living with HIV (PLWH) and their pathogenesis isn't completely understood. We aimed to explore the association between plasma and CSF markers of blood-brain barrier (BBB) impairment and HAND in untreated PLWH.

Design: Cross-sectional study.

Methods: We enrolled untreated PLWH, who underwent blood exams and lumbar puncture to measure inflammation (IL-15, TNF-α), BBB damage (zonulin and tight junction proteins, TJs: occludin, claudin-5) and endothelial adhesion molecules (VCAM-1, ICAM-1). A comprehensive neurocognitive battery was used to diagnose HAND (Frascati criteria).

Results: Twenty-one patients (21/78, 26,9%) patients presented HAND (100% ANI). HAND patients displayed more frequently non-CNS AIDS-defining conditions, lower nadir CD4+ T-cells and increased CD4+ T-cell exhaustion (lower CD4+CD127+ and CD4+CD45RA+ T cells percentages), in comparison to subjects without cognitive impairment. Furthermore, HAND was characterized by higher plasma inflammation (IL-15), but lower CSF levels of biomarkers of BBB impairment (zonulin and occludin). The association between BBB damage with HAND was confirmed by fitting a multivariable logistic regression. CSF/plasma endothelial adhesion molecules weren't associated with HAND, but with a poor performance in different cognitive domains.

Conclusions: By showing heightened inflammation and BBB impairment, our study suggests loss of BBB integrity as a possible factor contributing to the development of HAND in untreated PLWH.