P12. CNS immune activation still present despite > 10 years of effective antiretroviral therapy of HIV-1

Gustaf Hammarlund1, Åsa Mellgren2, Dietmar Fuchs3, Henrik Zetterberg4, 5, Lars Hagberg1, Staffan Nilsson6, Aylin Yilmaz1, Arvid Edén1, Magnus Gisslén1.
Affiliates: 1Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, 2Clinic of Infectious Diseases, South Älvsborg Hospital, Borås, Sweden, 3Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria, 4Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden, 5Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK5, 6Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden

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Background
Antiretroviral therapy (ART) effectively supresses viral load in plasma and cerebrospinal fluid (CSF) and substantially decreases the intrathecal immune activation commonly found in untreated HIV. Signs of low-grade intrathecal immune activation can, however, be found in a substantial proportion of people living with HIV (PLHIV) even after initiation of ART. CSF neopterin, a well characterized marker of microglial/macrophage activation, has been associated with HIV-associated neurocognitive disorders (HAND) in untreated as well in patients on suppressive ART. The aim of this study was to examine residual intrathecal immune activation in correlation to signs of neuronal injury and neurocognitive impairment in PLHIV virally suppressed on ART for more than 10 years.

Methods
Neurologically asymptomatic PLHIV on ART ≥ 10 years with plasma HIV-RNA levels 10 years, 55% of PLHIV continue to show signs of macrophage/microglia activation in the CNS. Further longitudinal studies are needed to explore if this long-term low-grade CNS inflammation has any clinical implications, however, it is reassuring that no association was found with neurocognitive performance or signs of neuronal injury.

Results
Neopterin decreased significantly in both plasma (from in median 25.1 (IQR 13.3-37.7) to 7.40 (IQR 4.9-10.1) nmol/L) and in CSF (from in median 18.3 (IQR 10.9-28.8) – 5.95 (IQR 4.6-7.9) nmol/L) after treatment initiation. Twelve of 22 (55 %) participants still had CSF neopterin above the upper normal reference limit (5.8 nmol/L) despite > 10 years of ART.
No significant correlations were found between CSF neopterin and CSF NFL or neurocognitive performance. No difference was seen in CSF NFL or neurocognitive performance in subjects with normal compared to increased CSF neopterin.

Conclusions
ART significantly decreases intrathecal immunoactivation, but, despite effective treatment for > 10 years, 55% of PLHIV continue to show signs of macrophage/microglia activation in the CNS. Further longitudinal studies are needed to explore if this long-term low-grade CNS inflammation has any clinical implications, however, it is reassuring that no association was found with neurocognitive performance or signs of neuronal injury.