Effects of early HIV infection and combination antiretroviral therapy on intrinsic brain activity: a cross-sectional resting-state fMRI study

Objective: To investigate effects of early HIV infection and combination antiretroviral therapy (cART) on intrinsic brain activity by using amplitude of low-frequency fluctuation (ALFF) analysis. Patients and methods: Forty-nine HIV patients, including 26 with cART (HIV+/cART+) and 23 treatment-naïve (HIV+/cART–), and 25 matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging examination. ALFF values were compared by using one-way ANOVA tests with Analysis of Functional NeuroImages (AFNI)’s 3dClustSim correction (voxel p<0.005, α<0.05). In addition, the ALFF values of brain regions that showed significant differences among the three groups were correlated with clinical and neuropsychological variables in both groups of patients by using Spearman correlation analysis. Results: ANOVA analysis showed that statistic difference of ALFF values among three groups was located in the occipital cortex. Post hoc analysis showed a decrease in occipital ALFF value in HIV patients compared to HC, but showed no difference of occipital ALFF between HIV+/cART+ and HIV+/cART–. Additionally, compared with HC, HIV+/cART+ exhibited higher ALFF in the right caudate and frontoparietal cortex, and HIV+/cART- showed higher ALFF in the bilateral caudate. HIV+/cART+ demonstrated higher ALFF values in auditory cortex than HIV+/cART–. Moreover, ALFF values in the right occipital cortex were positively associated with CD4(+)/CD8(+) ratio and executive function in HIV+/cART–. Conclusion: Early HIV-infected individuals presented reduced spontaneous brain activity in the occipital cortex. cART appeared to be ineffective in halting the HIV-induced neurodegeneration but might delay the progression of neural dysfunction to some extent. ALFF might be a potential biomarker in monitoring the effects of HIV and cART on brain function.