Abstract
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.
Highlights
Introduction published maps and institutional affilThere are approximately 38 million people living with HIV worldwide [1], out of which 20–50% are estimated to develop a certain degree of cognitive impairment [2].Despite combination antiretroviral therapy that has substantially contributed to reducing the HIV-related complications and mortality, HIV-associated neurocognitive disorders (HAND) continue to be relevant, especially considering their prevalence on a global scale [3]
Up to 22% of asymptomatic HIV-positive subjects, 50% of patients suffering from AIDS and up to 100% of patients with HIV-associated dementia (HAD) showed an increased BBB permeability [4]
Monocyte transit across the BBB is a pivotal process in HIV central nervous system (CNS) infection [5] and several mechanisms have been involved in the pathogenesis of HAND, including neuroinflammation, antiretroviral neurotoxicity, tight junction iations
Summary
Despite combination antiretroviral therapy (cART) that has substantially contributed to reducing the HIV-related complications and mortality, HIV-associated neurocognitive disorders (HAND) continue to be relevant, especially considering their prevalence on a global scale [3]. Blood–brain barrier impairment (BBBi) may play a crucial role in the pathogenesis of HAND. In this regard, up to 22% of asymptomatic HIV-positive subjects, 50% of patients suffering from AIDS and up to 100% of patients with HIV-associated dementia (HAD) showed an increased BBB permeability [4]. Monocyte transit across the BBB is a pivotal process in HIV central nervous system (CNS) infection [5] and several mechanisms have been involved in the pathogenesis of HAND, including neuroinflammation, antiretroviral neurotoxicity, tight junction iations
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