Abstract
Cocaine use is disproportionately prevalent in people with HIV (PWH) and is known to potentiate HIV neuropathogenesis. As both HIV and cocaine have well-documented cortico-striatal effects, PWH who use cocaine and have a history of immunosuppression may exhibit greater FC deficits compared to PWH without these conditions. However, research investigating the legacy effects of HIV immunosuppression (i.e., a history of AIDS) on cortico-striatal functional connectivity (FC) in adults with and without cocaine use is sparse. Resting-state functional magnetic resonance imaging (fMRI) and neuropsychological assessment data from 273 adults were analyzed to examine FC in relation to HIV disease: HIV-negative (n = 104), HIV-positive with nadir CD4 ≥ 200 (n = 96), HIV-positive with nadir CD4 < 200 (AIDS; n = 73), and cocaine use (83 COC and 190 NON). Using independent component analysis/dual regression, FC was assessed between the basal ganglia network (BGN) and five cortical networks: dorsal attention network (DAN), default mode network, left executive network, right executive network, and salience network. There were significant interaction effects such that AIDS-related BGN-DAN FC deficits emerged in COC but not in NON participants. Independent of HIV, cocaine effects emerged in FC between the BGN and executive networks. Disruption of BGN-DAN FC in AIDS/COC participants is consistent with cocaine potentiation of neuro-inflammation and may be indicative of legacy HIV immunosuppressive effects. The current study bolsters previous findings linking HIV and cocaine use with cortico-striatal networking deficits. Future research should consider the effects of the duration of HIV immunosuppression and early treatment initiation.