Cerebrospinal fluid pleocytosis is associated with HIV-1 neuroinvasion during acute infection

Abstract

Objective: HIV-1 invades the brain within days post-transmission. This study quantitated cerebrospinal fluid (CSF) white blood cell count (WBC) and investigated whether it associated with plasma and CSF HIV-1 RNA during untreated acute HIV infection (AHI). Design: Seventy participants underwent lumbar puncture during Fiebig stages I–V AHI. Method: WBC and HIV-1 RNA with a lower limit of quantification (LLQ) of 80 copies/ml were measured in CSF. Results: Sixty-nine (99%) participants were men, with a median age of 26. Their blood CD4+ and CD8+ T-cell counts were 335 [interquartile range (IQR) 247–553) and 540 (IQR 357–802) cells/μl, respectively. Forty-five (64%) were in Fiebig stages III–V whereas 25 (36%) were in Feibig stages I–II. Fifty-two (74%) experienced acute retroviral syndrome. Median plasma and CSF HIV-1 RNA were 6.10 (IQR 5.15–6.78) and 3.15 (IQR 1.90–4.11) log10 copies/ml, respectively. Sixteen (23%) CSF samples had HIV-1 RNA below LLQ. Median CSF WBC was 2.5 (IQR 1–8) cells/μl. CSF pleocytosis (WBC >5) was observed in 33% and was only present in CSF samples with detectable HIV-1 RNA. The frequencies of CSF pleocytosis during Fiebig stages III–V and among CSF samples of higher viral load (>1000 copies/ml) were 42 and 45%, respectively. Pleocytosis independently associated with CSF HIV-1 RNA in multivariate analysis [adjusted coefficient: 0.79, 95% confidence interval (CI) 0.41–1.14), P < 0.001] and a lower plasma to CSF HIV-1 RNA ratio (P < 0.001). Conclusion: CSF pleocytosis was present in one-third of participants with AHI. It associated with higher CSF HIV-1 RNA and a lower plasma to CSF HIV-1 RNA ratio, suggesting a potential association with HIV-1 neuroinvasion.