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.
Background
The aim of this large multicenter study was to determine variations in cerebrospinal fluid (CSF) HIV-RNA in different phases of untreated HIV-1 infection and its associations with plasma HIV-RNA and other biomarkers.
Methods
Treatment naïve adults with available CSF HIV-RNA quantification were included and divided into groups representing significant disease phases. Plasma HIV-RNA, CSF white blood cell count (CSF WBC), neopterin, and albumin ratio were included when available.
Results
1.018 patients were included. CSF HIV-RNA was in median (IQR) 1.03 log10 (0.37–1.86) copies/mL lower than in plasma, and correlated with plasma HIV-RNA (r=0.44, p< 0.01), neopterin concentration in CSF (r=0.49, p< 0.01) and in serum (r=0.29, p< 0.01), CSF WBC (r=0.34, p< 0.01) and albumin ratio (r=0.25, p< 0.01). CSF HIV-RNA paralleled plasma HIV-RNA in all groups except neuroasymptomatic patients with advanced immunodeficiency (CD4 < 200) and patients with HIV-associated dementia (HAD) or opportunistic CNS infections.
Patients with HAD had the highest CSF HIV-RNA (in median [IQR] 4.73 (3.84–5.35) log10 copies/mL). CSF > plasma discordance was found in 126 of 972 individuals (13%) and varied between groups, from 1% in primary HIV, 11% in neuroasymptomatic groups, up to 30% of patients with HAD.
Conclusions
Our study confirms previous smaller observations of variations in CSF HIV-RNA in different stages of HIV disease. Overall, CSF HIV-RNA was approximately 1 log10 copies/mL lower in CSF than in plasma, but CSF discordance was found in a substantial minority of subjects, most commonly in patients with HAD, indicating increasing CNS compartmentalization paralleling disease progression.
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