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

Hasan Sari; Riccardo Galbusera; Guillaume Bonnier; Yang Lin; Zeynab Alshelh; Angel Torrado-Carvajal; Shibani S Mukerji; Eva M Ratai; Rajesh T Gandhi; Jacqueline T Chu; Oluwaseun Akeju; Vwaire Orhurhu; Andrew N Salvatore; Janet Sherman; Douglas S Kwon; Bruce Walker; Bruce Rosen; Julie C Price; Lauren E Pollak; Marco L Loggia; Cristina Granziera

doi:10.1212/NXI.0000000000001144

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

Neurol Neuroimmunol Neuroinflamm. 2022 Feb 9;9(2):e1144. doi: 10.1212/NXI.0000000000001144. Print 2022 Mar.

Authors

Hasan Sari¹, Riccardo Galbusera¹, Guillaume Bonnier¹, Yang Lin¹, Zeynab Alshelh¹, Angel Torrado-Carvajal¹, Shibani S Mukerji¹, Eva M Ratai¹, Rajesh T Gandhi¹, Jacqueline T Chu¹, Oluwaseun Akeju¹, Vwaire Orhurhu¹, Andrew N Salvatore¹, Janet Sherman¹, Douglas S Kwon¹, Bruce Walker¹, Bruce Rosen¹, Julie C Price¹, Lauren E Pollak¹, Marco L Loggia¹, Cristina Granziera²

Affiliations

¹ From the MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging (H.S., Y.L., Z.A., A.T.-C., E.M.R., A.N.S., B.R., J.C.P., M.L.), Massachusetts General Hospital, Harvard Medical School, Charlestown; Neurologic Clinic and Policlinic (R.G., G.B., C.G.), Departments of Medicine, Clinical Research and Biomedical Engineering, University Hospital Basel and University of Basel, Switzerland; Translational Imaging in Neurology (ThINk) Basel (R.G., G.B., C.G.), Department of Biomedical Engineering, University Hospital Basel and University of Basel, Switzerland; Medical Image Analysis and Biometry Lab (A.T.-C.), Universidad Rey Juan Carlos, Madrid, Spain; Department of Neurology (S.S.M., R.T.G.), Infectious Diseases (J.T.C.), Department of Anesthesia (O.A., V.O.), and Department of Psychiatry (J.S., L.E.P.), Massachusetts General Hospital, Boston; and Ragon Institute of MGH (D.S.K., B.W.), MIT and Harvard, Cambridge, MA.
² From the MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging (H.S., Y.L., Z.A., A.T.-C., E.M.R., A.N.S., B.R., J.C.P., M.L.), Massachusetts General Hospital, Harvard Medical School, Charlestown; Neurologic Clinic and Policlinic (R.G., G.B., C.G.), Departments of Medicine, Clinical Research and Biomedical Engineering, University Hospital Basel and University of Basel, Switzerland; Translational Imaging in Neurology (ThINk) Basel (R.G., G.B., C.G.), Department of Biomedical Engineering, University Hospital Basel and University of Basel, Switzerland; Medical Image Analysis and Biometry Lab (A.T.-C.), Universidad Rey Juan Carlos, Madrid, Spain; Department of Neurology (S.S.M., R.T.G.), Infectious Diseases (J.T.C.), Department of Anesthesia (O.A., V.O.), and Department of Psychiatry (J.S., L.E.P.), Massachusetts General Hospital, Boston; and Ragon Institute of MGH (D.S.K., B.W.), MIT and Harvard, Cambridge, MA. cristina.granziera@usb.ch.

Abstract

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 [¹¹C]-PBR28 signal and quantitative MRI (qMRI) measures of brain tissue integrity such as T1 and T2 relaxation times (rts).

Methods: [¹¹C]-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 [¹¹C]-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 [¹¹C]-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). [¹¹C]-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), [¹¹C]-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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Anti-Retroviral Agents / pharmacology*
Brain Diseases* / diagnostic imaging
Brain Diseases* / drug therapy
Brain Diseases* / pathology
Brain Diseases* / virology
Cognitive Dysfunction* / diagnosis
Cognitive Dysfunction* / physiopathology
Female
HIV Infections* / diagnostic imaging
HIV Infections* / drug therapy
HIV Infections* / pathology
HIV Infections* / virology
HIV Non-Progressors*
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Multimodal Imaging
Neuroimaging*
Neuroinflammatory Diseases* / diagnostic imaging
Neuroinflammatory Diseases* / drug therapy
Neuroinflammatory Diseases* / pathology
Neuroinflammatory Diseases* / virology
Positron-Emission Tomography

Substances

Anti-Retroviral Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding