Microglial activation is inversely associated with cognition in individuals living with HIV on effective antiretroviral therapy

Objective: Despite viral suppression, HIV-associated cognitive impairment persists and may be partially due to persistent immune signalling by cells of the myeloidlineage. Here, we aimed to understand the contribution of activated microglia located in vulnerable brain regions (e.g. frontal, subcortical) of HIV-infected, virally suppressed (HIV+VS) individuals in relation to cognitive and motor function. Design: Twenty-one HIV+VS individuals underwent PET with [¹¹C]DPA-713 to image the translocator protein 18 kDa (TSPO), a marker of microglial activation, and completed a comprehensive neuropsychological test battery. Methods: Multivariable linear regressions were used to examine the contribution of [¹¹C]DPA-713 binding to cognitive performance. Results: Higher [¹¹C]DPA-713 binding was associated with lower cognition among HIV+VS individuals. [¹¹C]DPA-713 binding in middle frontal gyrus/frontal cortex, hippocampus/temporal cortex and occipital cortex was inversely associated with performance on a number of cognitive domains, including verbal memory, processing speed/attention/concentration, executive function, working memory and motor function. [¹¹C]DPA-713 binding in parietal cortex, cerebellum and thalamus was associated with only specific cognitive domains including visual construction and verbal memory. Binding was not associated with global cognitive performance. Conclusion: The findings add to the growing body of evidence that immune-mediated brain injury may contribute to domain specific, HIV-associated, cognitive vulnerabilities despite viral suppression.