Persistent central nervous system immune activation following more than 10 years of effective HIV antiretroviral treatment
Artikel i vetenskaplig tidskrift, 2018

Objective: 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 for more than 10 years. Design/methods: 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. Pretreatment samples were available for 14 patients. Cognitive function was assessed by CogState at follow-up. Results: 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 followup. 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. Conclusion: Although CSF neopterin decreased significantly, more than 50% of the patients had CSF concentrations above the upper normal reference value despite more than 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.



Neurofilament light protein


Antiretroviral therapy

Central nervous system

Cerebrospinal fluid


Gustaf Ulfhammer

Göteborgs universitet

Arvid Edén

Göteborgs universitet

Sa Mellgren

Södra Älvsborgs Sjukhus (SÄS)

Göteborgs universitet

D. Fuchs

Medizinische Universität Innsbruck

Henrik Zetterberg

Sahlgrenska universitetssjukhuset

Göteborgs universitet

UK Dementia Research Institute

University College London (UCL)

L. Hagberg

Göteborgs universitet

Staffan Nilsson

Chalmers, Matematiska vetenskaper, Tillämpad matematik och statistik

Aylin Yilmaz

Göteborgs universitet

Magnus Gisslen

Göteborgs universitet


0269-9370 (ISSN)

Vol. 32 15 2171-2178



Övrig annan medicin och hälsovetenskap




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