ObjectiveEven with successful combination antiretroviral therapy (cART), patients with human immunodeficiency virus positive (HIV+) continue to present structural alterations and neuropsychological impairments. The purpose of this study is to investigate structural brain connectivity alterations and identify the hub regions in HIV+ patients with fully suppressed plasma viral loads. MethodsIn this study, we compared the brain structural connectivity in 48 patients with HIV+ treated with a combination of antiretroviral therapy and 48 healthy controls, using diffusion tensor imaging. Further comparisons were made in 24 patients with asymptomatic neurocognitive impairment (ANI) and 24 individuals with non-HIV-associated neurocognitive disorders forming a subset of HIV+ patients. The graph theory model was used to establish the topological metrics. Rich-club analysis was used to identify hub nodes across groups and abnormal rich-club connections. Correlations of connectivity metrics with cognitive performance and clinical variables were investigated as well. ResultsAt the regional level, HIV+ patients demonstrated lower degree centrality (DC), betweenness centrality (BC), and nodal efficiency (NE) at the occipital lobe and the limbic cortex; and increased BC and nodal cluster coefficient (NCC) in the occipital lobe, the frontal lobe, the insula, and the thalamus. The ANI group demonstrated a significant reduction in the DC, NCC, and NE in widespread brain regions encompassing the occipital lobe, the frontal lobe, the temporal pole, and the limbic system. These results did not survive the Bonferroni correction. HIV+ patients and the ANI group had similar hub nodes that were mainly located in the occipital lobe and subcortical regions. The abnormal connections were mainly located in the occipital lobe in the HIV+ group and in the parietal lobe in the ANI group. The BC in the calcarine fissure was positively correlated with complex motor skills. The disease course was negatively correlated with NE in the middle occipital gyrus. ConclusionThe results suggest that the occipital lobe and the subcortical regions may be important in structural connectivity alterations and cognitive impairment. Rich-club analysis may contribute to our understanding of the neuropathology of HIV-associated neurocognitive disorders.