Multimodal Investigation of Neuroinflammation in Aviremic Patients With HIV on Antiretroviral Therapy and HIV Elite Controllers

BACKGROUND AND OBJECTIVES: The presence of HIV in the CNS has been related to chronic immune activation and cognitive dysfunction. The aim of this work was to investigate (1) the presence of neuroinflammation in aviremic people with HIV (PWH) on therapy and in nontreated aviremic PWH (elite controllers [ECs]) using a translocator protein 18 kDa radioligand; (2) the relationship between neuroinflammation and cognitive function in aviremic PWH; and (3) the relationship between [(11)C]-PBR28 signal and quantitative MRI (qMRI) measures of brain tissue integrity such as T1 and T2 relaxation times (rts). METHODS: [(11)C]-PBR28 (standard uptake value ratio, SUVR) images were generated in 36 participants (14 PWH, 6 ECs, and 16 healthy controls) using a statistically defined pseudoreference region. Group comparisons of [(11)C]-PBR28 SUVR were performed using region of interest–based and voxelwise analyses. The relationship between inflammation, qMRI measures, and cognitive function was studied. RESULTS: In region of interest analyses, ECs exhibited significantly lower [(11)C]-PBR28 signal in the thalamus, putamen, superior temporal gyrus, prefrontal cortex, and cerebellum compared with the PWH. In voxelwise analyses, differences were observed in the thalamus, precuneus cortex, inferior temporal gyrus, occipital cortex, cerebellum, and white matter (WM). [(11)C]-PBR28 signal in the WM and superior temporal gyrus was related to processing speed and selective attention in PWH. In a subset of PWH (n = 12), [(11)C]-PBR28 signal in the thalamus and WM regions was related to a decrease in T2 rt and to an increase in T1 rt suggesting a colocalization of increased glial metabolism, decrease in microstructural integrity, and iron accumulation. DISCUSSION: This study casts a new light onto the role of neuroinflammation and related microstructural alterations of HIV infection in the CNS and shows that ECs suppress neuroinflammation more effectively than PWH on therapy.