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Persistent CNS immune activation following > 10 years of effective HIV antiretroviral treatment.

Journal article
Authors Gustaf Ulfhammer
Arvid Edén
Åsa Mellgren
Dietmar Fuchs
Henrik Zetterberg
Lars Hagberg
Staffan Nilsson
Aylin Yilmaz
Magnus Gisslén
Published in AIDS (London, England)
Volume 32
Issue 15
Pages 2171–2178
ISSN 1473-5571
Publication year 2018
Published at Department of Mathematical Sciences, Applied Mathematics and Statistics
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Institute of Biomedicine, Department of Infectious Medicine
Pages 2171–2178
Language en
Subject categories Neurochemistry


Low-grade immune activation is common in people living with HIV (PLHIV), despite long-term viral suppression by antiretroviral therapy (ART). The clinical significance of this activation remains unclear. The aim of this study was to examine residual intrathecal immune activation in relation to signs of neuronal injury and neurocognitive impairment in PLHIV who had been virally suppressed on ART > 10 years.Twenty neuroasymptomatic PLHIV on suppressive ART for a median of 13.2 years were retrospectively identified from the longitudinal prospective Gothenburg HIV cerebrospinal fluid (CSF) study. HIV-RNA, neopterin, and neurofilament light protein (NFL) levels were measured in paired plasma and CSF samples. Pre-treatment samples were available for 14 subjects. Cognitive function was assessed by CogState at follow-up.CSF neopterin decreased from a median (IQR) of 17.8 (10.6-29.7) to 6.1 (4.6-8.0) nmol/L during treatment (p < 0.001). In 11 out of 20 participants (55%), CSF neopterin levels were above the upper normal reference limit (5.8 nmol/L) at follow-up. Age-adjusted CSF NFL decreased to within normal levels from a median of (IQR) 1179 (557-2707) to 415 (292-610) ng/L (p < 0.001). No significant correlations were found between CSF neopterin and CSF NFL or neurocognitive performance.Although CSF neopterin decreased significantly, >50% of the subjects had CSF concentrations above the upper normal reference value despite >10 years of suppressive ART. We found no correlation between CSF neopterin, CSF NFL or neurocognitive performance at follow up, indicating that low grade immune activation during suppressive ART may be clinically benign.

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