Abstract
BackgroundBlood-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.MethodsWe 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).ResultsWe 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.ConclusionThese findings indicate that ART improves and possibly normalizes BBB integrity in both neuroasymptomatic HIV-infected individuals and in patients with HAD.
Highlights
Blood-brain barrier (BBB) injury is prevalent in patients with HIV-associated dementia (HAD) and is a frequent feature of HIV encephalitis
BBB integrity is impaired in patients with HIV encephalitis, and the BBB has been shown to play an important role in the pathogenesis and development of HAD [1, 12,13,14], the process has not been fully understood
We have previously determined that 68% of individuals with HAD had signs of BBB impairment [4, 15], but we found no association between the level of immune suppression and elevated albumin ratio in untreated neuroasymptomatic individuals out of whom 16% had signs of BBB impairment [3, 4]
Summary
Blood-brain barrier (BBB) injury is prevalent in patients with HIV-associated dementia (HAD) and is a frequent feature of HIV encephalitis. 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. Several studies have shown an association between BBB integrity, intrathecal immune activation and CSF concentrations of NfL [4, 6,7,8,9], implying an association between CNS inflammation, BBB impairment, and neuronal injury. Prior to the introduction of modern antiretroviral therapy (ART), approximately 30 to 40% of patients with AIDS developed HIV-associated dementia (HAD) [10, 11]. We have previously determined that 68% of individuals with HAD had signs of BBB impairment [4, 15], but we found no association between the level of immune suppression and elevated albumin ratio in untreated neuroasymptomatic individuals out of whom 16% had signs of BBB impairment [3, 4]
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