Journal article

Intact HIV Proviruses Persist in the Brain Despite Viral Suppression with ART

CR Cochrane, TA Angelovich, SJ Byrnes, E Waring, AC Guanizo, GS Trollope, J Zhou, J Vue, L Senior, E Wanicek, JJ Eddine, MJ Gartner, TA Jenkins, PR Gorry, BJ Brew, SR Lewin, JD Estes, M Roche, MJ Churchill

Annals of Neurology | WILEY | Published : 2022

Abstract

Objective: Human immunodeficiency virus (HIV) persistence in blood and tissue reservoirs, including the brain, is a major barrier to HIV cure and possible cause of comorbid disease. However, the size and replication competent nature of the central nervous system (CNS) reservoir is unclear. Here, we used the intact proviral DNA assay (IPDA) to provide the first quantitative assessment of the intact and defective HIV reservoir in the brain of people with HIV (PWH). Methods: Total, intact, and defective HIV proviruses were measured in autopsy frontal lobe tissue from viremic (n = 18) or virologically suppressed (n = 12) PWH. Total or intact/defective proviruses were measured by detection of HIV..

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Grants

Awarded by National Institutes of Health


Funding Acknowledgements

This work was supported by the National Health and Medical Research Council, Australia 1183032 (to M.J.C., J.D.E., M.R., and P.R.G.), The Jack Brockhoff Foundation JBF Grant number 4501 - 2018 (to T.A.A. and M.J.C.), and the Melbourne HIV Cure Consortium (to M.R. and C.R.C.). Research reported in this publication was supported by the National Institute On Drug Abuse of the National Institutes of Health under Award Number R21DA055489 (to M.J.C., M.R., and T.A.A.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. S.R.L. is supported by a National Health and Medical Research Council, Australia Practitioner Fellowship (S.R.L.). All authors gratefully acknowledge the support from the NNTC and this publication was made possible from NIH funding through the NIMH and NINDS Institutes by the following grants: Texas NeuroAIDS Research Center: U24MH100930, California NeuroAIDS Tissue Network: U24MH100928, National Neurological AIDS Bank: U24MH100929, Manhattan HIV Brain Bank: U24MH100931, and Data Coordinating Center: U24MH100925. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the NNTC or NIH. The authors thank Dr Anna Hearps and Dr Michelle Wong (Burnet Institute, Australia) for providing reagents. Open access publishing facilitated by RMIT University, as part of the Wiley -RMIT University agreement via the Council of Australian University Librarians.