Abstract
BackgroundThe long-term neurological consequences of HIV infection and treatment are not yet completely understood. In this study we examined the prevalence of cerebral metabolic abnormalities among a cohort of neurologically intact HIV patients with fully suppressed HIV viral loads. Concomitant analyses of circulating brain derived neurotrophic factor (BDNF) were performed to correlate these abnormalities with potential signs of neuro-regenerating/protective activity, and concomitant analyses of circulating tumour necrosis factor (TNF) α, interleukin (IL) 6, and soluble urokinase plasminogen activator receptor (suPAR) were performed to correlate these abnormalities with potential signs of neurodegenerative processes.MethodsThe study population consisted of HIV-positive patients known to be infected for more than 5 years and on antiretroviral (ARV) treatment for a minimum of three years with no history of virological failure, a CD4 count above 200 × 106 cells/l and no other co-morbidities. The distribution of the regional cerebral metabolic rate of glucose metabolism was measured using fluorine-18-flourodeoxyglucose positron emission tomography (FDG-PET) scanning. The PET scans were evaluated for individual pathology using Neurostat software and for group pathology using statistical parametric mapping (SPM). Circulating levels of BDNF, TNF α, IL-6 and suPAR were measured by ELISA techniques.ResultsMore than half (55%) of the patients exhibited varying severities of mesial frontal reduction in the relative metabolic rate of glucose. Compared to healthy subjects, the patients with abnormal FDG-PET scanning results had a shorter history of known HIV infection, fewer years on antiretroviral therapy and higher levels of circulating TNF α and IL-6 (p = 0.08).ConclusionA large proportion of optimally treated HIV patients exhibit cerebral FDG-PET scanning abnormalities and elevated TNF α and IL-6 levels, which may indicate imminent neuronal damage. The neuroprotective effect of early ARV treatment should be considered in future prospective follow-up studies.
Highlights
The long-term neurological consequences of Human immunodeficiency virus (HIV) infection and treatment are not yet completely understood
Patients with acute HIV infection may present with symptoms of aseptic meningitis, and pleocytosis of the cerebrospinal fluid CSF is a frequent finding among HIV patients [1]
In a small pilot study, we found that a surprisingly large fraction of optimally treated HIV patients show minor abnormalities in the relative metabolic rates of glucose metabolism in brain as visualized by fluorine-18-flourodeoxyglucose positron emission tomography (FDG-PET) scanning [6]
Summary
The long-term neurological consequences of HIV infection and treatment are not yet completely understood. Before the era of combined active antiretroviral (ARV) therapy, a substantial number of those patients who survived despite low levels of CD4-positive lymphocytes developed AIDS dementia abnormalities in the relative metabolic rates of glucose metabolism in brain as visualized by fluorine-18-flourodeoxyglucose positron emission tomography (FDG-PET) scanning [6]. These abnormalities resemble signs of imminent neurodegeneration [7,8]. The aim of this study was to perform cerebral FDG-PET scanning on a larger number of patients, and to correlate potential abnormalities with levels of circulating pro-inflammatory cytokines that have been associated with neurodegenerative conditions [9,10,11], and with a potential indicator of neuro-regenerative/protective activities: brain derived neurotrophic factor (BDNF) [12,13]
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