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Background This prospective study characterizes the structural and metabolic cerebral correlates of cognitive impairments found in a preclinical setting that considers the lifestyle of young European men exposed to human immunodeficiency virus (HIV), including recreational drugs. Methods Simultaneous structural brain magnetic resonance imaging (MRI) and positron emission tomography using [18F]-fluorodeoxyglucose (FDG-PET) were acquired on a hybrid PET-MRI system in 23 asymptomatic young men having sex with men with HIV (HIVMSM; mean age, 33.6 years [range, 23–60 years]; normal CD4+ cell count, undetectable viral load). Neuroimaging data were compared with that of 26 young seronegative men under HIV preexposure prophylaxis (PrEPMSM), highly well matched for age and lifestyle, and to 23 matched young seronegative men (controls). A comprehensive neuropsychological assessment was also administered to the HIVMSM and PrEPMSM participants. Results HIVMSM had lower performances in executive, attentional, and working memory functions compared to PrEPMSM. No structural or metabolic differences were found between those 2 groups. Compared to controls, HIVMSM and PrEPMSM exhibited a common hypometabolism in the prefrontal cortex that correlated with the level of recreational drug use. No structural brain abnormality was found. Conclusions Abnormalities of brain metabolism in our population of young HIVMSM mainly relate to recreational drug use rather than HIV per se. A complex interplay between recreational drugs and HIV might nevertheless be involved in the cognitive impairments observed in this population.