In this cross-sectional study we used magnetic resonance imaging (MRI)-based voxel based morphometry (VBM) in a sample of HIV positive patients to detect structural gray and white matter changes. Forty-eight HIV positive subjects with (n = 28) or without (n = 20) cognitive deficits (mean age 48.5 ± 9.6 years) and 48 age- and sex-matched HIV negative controls underwent MRI for VBM analyses. Clinical testing in HIV patients included the HIV dementia scale (HDS), Unified Parkinson's Disease Rating Scale (UPDRS) and the grooved pegboard test. Comparing controls with HIV positive patients with cognitive dysfunction (n = 28) VBM showed gray matter decrease in the anterior cingulate and temporal cortices along with white matter reduction in the midbrain region. These changes were more prominent with increasing cognitive decline, when assigning HIV patients to three cognitive groups (not impaired, mildly impaired, overtly impaired) based on performance in the HIV dementia scale. Regression analysis including all HIV positive patients with available data revealed that prefrontal gray matter atrophy in HIV was associated with longer disease duration (n = 48), while motor dysfunction (n = 48) was associated with basal ganglia gray matter atrophy. Lower CD4 cell count (n = 47) correlated with decrease of occipital gray matter. Our results provide evidence for atrophy of nigro-striatal and fronto-striatal circuits in HIV. This pattern of atrophy is consistent with motor dysfunction and dysexecutive syndrome found in HIV patients with HIV-associated neurocognitive disorder.