<p>Human immunodeficiency virus (HIV) negatively impacts behavioral health and is co-morbid with neurocognitive and psychiatric disorders, most notably substance use disorder (SUD). Neuroimaging studies repeatedly show diminished functional connectivity in people living with HIV (PLWH). However, previous studies appear to disregard any potential for HIV/SUD co-morbidities, an oversight that represents a potential confound in HIV-related neuroimaging literature. Further, the functional connectivity of limbic neural substrates underlying reward and SUD (e.g., nucleus accumbens, amygdala, and hippocampus) remain unexplored in HIV. Here, we obtained resting-state functional magnetic resonance imaging (rsfMRI) data from a small population of HIV-positive people with no history of SUD. Functional connectivity in people with HIV was generally reduced relative to controls, with the greatest differences occurring between visual cortex and cerebellar vermis and nodules also associated with non-motor functions of cerebellum. Seed-based analyses of left and right nucleus accumbens (NAcc) and hippocampus (Hippo) yielded robust connections with the default mode network in controls. In PLWH, connectivity between NAcc or Hippo as seed recruited the default mode and inferior temporal networks to a lesser extent. Similar seed-based analyses of the amygdala in controls yielded robust connections with inferior temporal lobe regions rather than the default mode network, and exhibited anti-correlations with the executive network. Our results suggest that (1) people with HIV and no SUD history show reduced overall functional connectivity relative to controls, consistent with previous rsfMRI studies of people with HIV, and (2) this reduced connectivity in people with HIV extends to limbic structures underlying reward, even in the absence of SUD.</p>