Apathy is a cluster of symptoms that include a reduction in self-initiated, goaldirected behavior, and a lack of motoric, emotional, and cognitive motivation. It has been recognized as a clinical manifestation of HIV infection, but has received limited empirical attention. Previous studies of other neurologic groups indicate that apathy is associated with poor treatment response, deficits in everyday functioning, lower quality of life, and worse global cognitive functioning. HIV-associated brain pathology involves frontostriatal circuits, which are also implicated in the expression of apathy. Three studies were conducted to examine the neural, psychiatric (e.g., depression), and functional correlates of apathy in HIV infection. In all three studies, self-reported ratings of apathy were obtained using the Frontal Systems Behavior Scale (FrSBe). In the first investigation, relative to seronegative comparison subjects, HIV+ persons reported higher levels of apathy. Independent of major depressive disorder and other disease covariates, apathy ratings were found to be significantly associated with increased cognitive complaints and dependence in activities of daily living. Next, in a separate cohort, MRI Diffusion Tensor Imaging was used to examine the correspondence between these ratings and white matter abnormalities in the cortical nodes of the thalamocorticostriatal loop that reportedly subserves apathy. Results indicated that apathy severity was related to changes in neural integrity in frontomedial regions (i.e., anterior corona radiata, genu of corpus callosum, and orbitomedial prefrontal cortex). The strength of this relationship was associated with lower CD4 count, raising the possibility that dynamic changes in immune functioning may modify CNS pathology and consequent psychiatric outcomes. Finally, we examined whether depression, a comorbid psychiatric condition that is distinct from apathy, is related to change in apathy ratings across two visits in a cohort of 258 HIV+ participants. An inter-visit major depressive episode was associated with an increase in apathy ratings only in those participants who were not apathetic at their first visit. Regardless of initial apathy status, a new episode of major depression resulted in a higher risk of developing or maintaining clinically elevated apathy. These findings highlight the necessity to assess both depression and apathy, as they may interact to exacerbate psychiatric burden in HIVinfected cohorts. The findings of these three studies provide a greater understanding of the etiology of apathy and factors contributing to its expression in HIV+ individuals. Such information may help to identify patients at particular risk for functional impairments and potentially inform psychopharmacologic, behavioral, and HIV-treatment specific interventions that may mitigate apathy. This would be expected to help persons with HIV infection maintain better levels of functioning in their daily lives.