Persistent central nervous system immune activation following more than 10 years of effective HIV antiretroviral treatment

December 18, 2019

Authors: Gustaf Ulfhammer, Arvid Edén, Åsa Mellgren, Dietmar Fuchs, Henrik Zetterberg, Lars Hagberg, Staffan Nilsson, Aylin Yilmaz, Magnus Gisslén

Journal: Aids

DOI: 10.1097/QAD.0000000000001950

Year Published: 2018


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.


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.


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, 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.

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