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Biomarkers as indicators for the progression of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) remain still elusive. We performed a cross-sectional study to analyze the correlation between cognitive impairment, abnormalities in magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) markers of neurodegeneration in HIV-infected patients.We enrolled 94 patients (82 men and 12 women; mean age 45 ± 10 years) with HIV infection, but without opportunistic infections of the CNS. All patients underwent MRI and CSF analysis. The global pattern of white matter signal intensity abnormalities, the index of atrophy, the severity of periventricular white matter abnormalities, and the severity of basal ganglia signal changes were analyzed. We measured CSF markers of neurodegeneration (total tau, phospho-tau, beta-amyloid). The findings of this evaluation were correlated with demographic and infection parameters of the patients in blood and CSF.We found a highly significant correlation between the severity of global brain atrophy, basal ganglia signal changes, and cognitive impairment in HIV-infected patients. Furthermore, cognitive impairment was significantly correlated with total tau, but not with phospho-tau or A-beta-amyloid in CSF analysis.Our results confirm the significant correlation between MRI changes and cognitive impairment in HIV infection. Furthermore, we could show that global brain atrophy and signal changes in basal ganglia are the typical MRI pattern in HAND. The correlation between cognitive impairment and total tau, but not phospho-tau, supports the hypothesis that HAND are not a subtype of Alzheimer's dementia.