Blood Brain Barrier Impairment in HIV-Positive Naïve and Effectively Treated Patients: Immune Activation Versus Astrocytosis.
Blood brain barrier (BBB) damage is a common feature in central nervous system infections by HIV and it may persist despite effective antiretroviral therapy. Astrocyte involvement has not been studied in this setting. Patients were enrolled in an ongoing prospective study and subjects with central nervous system-affecting disorders were excluded. Patients were divided into two groups: treated subjects with cerebrospinal fluid (CSF) HIV RNA <50 copies/mL (CSF-controllers) and in late-presenters CD4+ T lymphocytes <100/uL. CSF biomarkers of neuronal or astrocyte damage were measured and compared to CSF serum-to-albumin ratio. 134 patients were included; 67 subjects in each group (50 %) with similar demographic characteristics (with the exception of older age in CSF controllers). CD4 (cells/uL), plasma and CSF HIV RNA (Log10copies/mL) were 43 (20-96), 5.6 (5.2-6) and 3.9 (3.2-4.7) in LPs and 439 (245-615), <1.69 (9 patients <2.6) and <1.69 in CSFc. BBB impairment was observed in 17 late-presenters (25.4 %) and in 9 CSF-controllers (13.4 %). CSF biomarkers were similar but for higher CSF neopterin values in late-presenters (2.3 vs. 0.6 ng/mL, p < 0.001). CSARs were associated with CSF neopterin (rho = 0.31, p = 0.03) and HIV RNA (rho = 0.24, p = 0.05) in late-presenters and with CSF tau (rho = 0.51, p < 0.001), p-tau (rho = 0.47, p < 0.001) and S100beta (rho = 0.33, p = 0.009) in CSF-controllers. In HAART-treated subjects with suppressed CSF HIV RNA, BBB altered permeability was associated with markers of neuronal damage and astrocytosis. Additional treatment targeting astrocytosis and/or viral protein production might be needed in order to reduce HIV effects in the central nervous system.
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at Ospedale Amedeo di Savoia, ASL TO2, Torino, Italy. andrea.calcagno@unito.it.
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Calcagno
Laboratory of Immunology, Ospedale Maria Vittoria, ASL TO2, Torino, Italy.
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Romito
Unit of Neurology, Ospedale Maria Vittoria, ASL TO2, Torino, Italy.
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Atzori
Laboratory of Microbiology and Molecular Biology, Ospedale Amedeo di Savoia, ASL TO2, Torino, Italy.
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Ghisetti
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at Ospedale Amedeo di Savoia, ASL TO2, Torino, Italy.
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Cardellino
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at Ospedale Amedeo di Savoia, ASL TO2, Torino, Italy.
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Audagnotto
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at Ospedale Amedeo di Savoia, ASL TO2, Torino, Italy.
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Scarvaglieri
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at Ospedale Amedeo di Savoia, ASL TO2, Torino, Italy.
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Lipani
Unit of Neurology, Ospedale Maria Vittoria, ASL TO2, Torino, Italy.
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Imperiale
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at Ospedale Amedeo di Savoia, ASL TO2, Torino, Italy.
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Di Perri
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at Ospedale Amedeo di Savoia, ASL TO2, Torino, Italy.
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Bonora
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D005911:Gliosis / Q000134:cerebrospinal fluid* / Q000276:immunology; D015658:HIV Infections / Q000134:cerebrospinal fluid* / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D019380:Anti-HIV Agents
Albumin ratio; Astrocytosis; Biomarkers; Blood brain barrier; S-100 beta