Cerebral white matter integrity during primary HIV infection

OBJECTIVE:: Inflammation and infection within the central nervous system is initiated during primary HIV infection (PHI), but the association of these processes with the integrity of brain white matter during PHI is unknown. DESIGN:: We used diffusion tensor imaging (DTI) in this prospective cross-sectional neuroimaging study to determine the extent of white matter involvement in early HIV infection. METHODS:: Antiretroviral-naive PHI (defined as <1 year after infection, n=62), chronic HIV infection (CHI, n=16), and HIV-uninfected (n=19) participants had DTI, laboratory, and neuropsychometric performance assessments. DTI metrics were examined using region of interest and whole brain voxelwise analyses. Linear mixed-effects models assessed correlations between DTI measures and laboratory and neuropsychometric performance values. RESULTS:: PHI participants were assessed at a median 4.1 months after estimated infection, and had median CD4 cell count of 573cells/μl, and HIV-1 RNA viral load of 4.5log10 copies/ml in plasma and 2.6log10 copies/ml in cerebrospinal fluid (CSF). DTI metrics in PHI individuals were similar to HIV- participants and correlated with disruptions in the blood-brain barrier (indicated by CSF/plasma albumin ratio and CSF protein). CHI participants had significant loss of white matter integrity that correlated with biomarkers of infection and inflammation (blood viral load, CD4 T-cell count, and neopterin, and CSF white blood cell). Within the PHI group, DTI metrics inversely correlated with increasing days since infection. CONCLUSION:: In individuals assessed during PHI, group DTI measures suggested relative preservation of white matter microstructural integrity, but were associated with disruption of the blood-brain barrier and estimated duration of infection..