Cerebrospinal Fluid viral load across the spectrum of untreated HIV-1 infection: a cross-sectional multi-center study

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.