De Francesco D, et al. - In people living with HIV (PLWH) vs comparable HIV-negative people, researchers assessed if differences in cognitive performance were mediated or moderated by depressive symptoms and lifestyle factors. Researchers performed a cross-sectional study of 637 older PLWH (aged ≥ 50 years), 340 younger PLWH (aged < 50 years) and 276 demographically matched HIV-negative controls (aged ≥ 50 years) enrolled in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study. Older and younger PLWH reported poorer overall cognitive scores than older HIV-negative controls following adjustment for sociodemographic factors. Both older and younger PLWH had a higher prevalence of moderate or severe depressive symptoms vs controls. The greater prevalence of depressive symptoms and recreational drug use reported by PLWH, in part, mediated the poorer cognitive performances in PLWH vs HIV-negative individuals.