Redistribution of brain glucose metabolism in people with HIV after antiretroviral therapy initiation.

OBJECTIVE We evaluated brain glucose metabolism in people living with HIV (PLWH) with [18F]-Fluoro-Deoxyglucose (FDG) PET/CT before and after antiretroviral therapy (ART) initiation.Design: We conducted a longitudinal study where ART-naive late-presenting untreated PLWH with CD4 counts < 100 cells/uL were prospectively assessed for FDG uptake at baseline and at 4-8 weeks (n=22) and 19-26 months (n = 11) following ART initiation. METHODS Relative uptake in the subcortical regions (caudate, putamen and thalamus) and cortical regions (frontal, parietal, temporal, and occipital cortices) were compared across time and correlated with biomarkers of disease activity and inflammation, in addition to being compared to a group of uninfected individuals (n = 10). RESULTS Before treatment initiation, putaminal and caudate relative FDG uptake values in PLWH were significantly higher than in uninfected controls. Relative putaminal and thalamic uptake significantly decreased shortly following ART initiation, while frontal cortex values significantly increased. FDG uptake changes correlated with changes in CD4 counts and VL, and, in the thalamus, with IL-6R and sCD14. Approximately two years following ART initiation, there was further decrease in subcortical relative uptake values, reaching levels below those of uninfected controls. CONCLUSIONS Our findings support pre-treatment basal ganglia and thalamic neuroinflammatory changes in PLWH, which decrease after treatment with eventual unmasking of long-term irreversible neuronal damage. Meanwhile, increased frontal cortex metabolism following ART initiation suggests reversible cortical dysfunction which improves with virologic control and increased CD4 counts. Early initiation of treatment after HIV diagnosis and secondary control of inflammation are thus necessary to halt neurological damage in PLWH.