|Authors: Pérez-Valero I, Letendre S, Heaton R, Ellis R, MCCutchan A, Simpson D, Deutsch R, Grant I, and the CHARTER Group|
|Abstract:Background: The association between levels of inflammatory biomarkers and CSF Viral Escape (CVE) is unexplored.
Methodology: Cross-sectional analysis performed to compare levels of inflammatory biomarkers in patients with and without CVE (HIV-RNA >50cop/mL in CSF and <50cop/mL in plasma). Individuals followed in two large HIV Cohorts, tested for CSF and blood biomarkers of immune activation (CXCL10, IL6, TNF-Alpha, MCP-1 and WBC) were included. Blood and CSF biomarkers along with demographics and HIV-related clinical data of patients with and without CVE were compared using multivariable logistic regression.
Results: 296 patients were evaluated: Mean age 46.6 years, 58% Caucasian, 87% male with a mean time of HIV-infection of 12.4 years and median CD4 nadir of 110 cells. CSF Viral Escape was detected in 8 patients (2,7%). Subjects’ characteristics were similar, regardless of CVE status, except for a longer HIV-infection (mean time 17.4 vs. 12.3 years; p=0.049) and a lower CD4 nadir (median 12 vs. 115 cells; p=0.038) associated with CVE. Median CSF CXCL10 levels were higher (6416 vs. 2771; p=0.011) while median plasma IL-6 levels were lower (1.56 vs. 2.97; p=0.049) in presence of CVE. Proportion of patients presenting CSF WBC pleocytosis was also higher (50% vs. 12.3%; p=0.002) in the CVE group. After logistic regression analysis, CXCL10 was the unique factor that remained independently associated with CVE (p<0.001).
Conclusions: CSF CXCL10 is elevated in patients with CVE, implying higher immune-activation and inflammation in their CNS, but our cross-sectional study cannot distinguish if these elevated levels are a cause or effect of CVE.|