Functional brain network reorganization in HIV infection

Background and Purpose To investigate the reorganization of the central nervous system provided by resting state-functional MRI (rs-fMRI), graph-theoretical analysis, and a newly developed functional brain network disruption index in patients with human immunodeficiency virus (HIV) infection. Methods Forty HIV-positive patients without neurological impairment and 20 age- and sex-matched healthy controls underwent rs-fMRI at 3T; blood sampling was obtained the same day to evaluate biochemical variables (absolute, relative, and nadir CD4 T-lymphocytes value and plasmatic HIV-RNA). From fMRI data, disruption indices, as well as global and local graph theoretical measures, were estimated and examined for group differences (HIV vs. controls) as well as for associations with biochemical variables (HIV only). Finally, all data (global and local graph-theoretical measures, disruption indices, and biochemical variables) were tested for putative differences across three patient groups based on the duration of combined antiretroviral therapy (cART). Results Brain function of HIV patients appeared to be deeply reorganized as compared to normal controls. The disruption index showed significant negative association with relative CD4 values, and a positive significant association between plasmatic HIV-RNA and local graph-theoretical metrics in the left lingual gyrus and the right lobule IV and V of right cerebellar hemisphere was also observed. Finally, a differential distribution of HIV clinical biomarkers and several brain metrics was observed across cART duration groups. Conclusion Our study demonstrates that rs-fMRI combined with advanced graph theoretical analysis and disruption indices is able to detect early and subtle functional changes of brain networks in HIV patients.