Asymptomatic Cerebrospinal Fluid HIV-1 Escape: Incidence and Consequences

Gustaf Ulfhammer; Aylin Yilmaz; Åsa Mellgren; Erika Tyrberg; Erik Sörstedt; Lars Hagberg; Johanna Gostner; Dietmar Fuchs; Henrik Zetterberg; Staffan Nilsson; Kristina Nyström; Arvid Edén; Magnus Gisslén

doi:10.1093/infdis/jiae555

Asymptomatic Cerebrospinal Fluid HIV-1 Escape: Incidence and Consequences

J Infect Dis. 2024 Nov 12:jiae555. doi: 10.1093/infdis/jiae555. Online ahead of print.

Authors

Gustaf Ulfhammer^{1

2}, Aylin Yilmaz^{1

2}, Åsa Mellgren^{1

2}, Erika Tyrberg^{1

2}, Erik Sörstedt^{1

2}, Lars Hagberg^{1

2}, Johanna Gostner³, Dietmar Fuchs⁴, Henrik Zetterberg^{5

6

7

8

9

10}, Staffan Nilsson¹¹, Kristina Nyström¹, Arvid Edén^{1

2}, Magnus Gisslén^{1

2

12}

Affiliations

¹ Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
² Region Västra Götaland, Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg, Sweden.
³ Institute of Medical Biochemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
⁴ Institute of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
⁵ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁶ Region Västra Götaland, Sahlgrenska University Hospital, Clinical Neurochemistry Laboratory, Mölndal, Sweden.
⁷ Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
⁸ Dementia Research Institute, London, UK.
⁹ Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.
¹⁰ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
¹¹ Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
¹² Public Health Agency of Sweden, Solna, Sweden.

PMID: 39531854
DOI: 10.1093/infdis/jiae555

Abstract

Background: The incidence and clinical relevance of asymptomatic cerebrospinal fluid escape (CSF-E) during antiretroviral therapy (ART) is uncertain. We examined the impact and incidence of asymptomatic CSF-E in a Swedish HIV cohort.

Methods: Neuroasymptomatic people living with HIV (PLWH) who have been on ART for at least six months with suppressed plasma viral load were followed longitudinally. CSF-E was defined as either increased CSF HIV-1 RNA with concurrent plasma suppression or as CSF HIV-1 RNA exceeding that in plasma when both were quantifiable. Paired CSF and plasma were analyzed for HIV-1 RNA, neopterin, neurofilament light protein (NfL), white blood cell (WBC) count, and albumin ratio.

Results: Asymptomatic CSF-E (cut-off 50 copies/mL) was found in 4/173 PLWH (2%) and 5/449 samples (1%). The corresponding proportions were 8% of PLWH and 4% for samples using a 20 copies/mL cut-off for CSF HIV-1 RNA. CSF-E samples (cut-off 20 copies/mL) had a 25% higher geometric mean of CSF neopterin (P = .01) and 8% higher albumin ratio (P = .04) compared to samples without CSF-E. No differences were observed in CSF NfL levels (P = .8). The odds ratio for increased CSF WBC (≥ 3 cells/μL) in samples with CSF-E was 3.9 (P = .004), compared to samples without elevated CSF viral load.

Conclusion: Asymptomatic CSF-E was identified in only four (2%) PLWH, with no cases of continuous CSF-E observed. Increased CSF HIV-1 RNA was associated with biomarkers of CNS immune activation and blood-brain-barrier impairment, but not with biomarkers of neuronal injury.

Keywords: HIV reservoirs; HIV-1; albumin ratio; cerebrospinal fluid; immune activation; neopterin; neurofilament protein light.