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

Autor: Catherine R. Cochrane, Thomas A. Angelovich, Sarah J. Byrnes, Emily Waring, Aleks C. Guanizo, Gemma S. Trollope, Jingling Zhou, Judith Vue, Lachlan Senior, Emma Wanicek, Janna Jamal Eddine, Matthew J. Gartner, Trisha A. Jenkins, Paul R. Gorry, Bruce J. Brew, Sharon R. Lewin, Jacob D. Estes, Michael Roche, Melissa J. Churchill
Rok vydání: 2022
Předmět:
Zdroj: Annals of neurology. 92(4)
ISSN: 1531-8249
Popis: 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).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 pol or the IPDA, respectively, through use of droplet digital polymerase chain reaction (ddPCR). HIV-seronegative individuals were included as controls (n = 6).Total HIV DNA was present at similar levels in brain tissues from untreated viremic and antiretroviral (ART)-suppressed individuals (median = 22.3 vs 26.2 HIV pol copies/10Our results demonstrate the first evidence for an intact, potentially replication competent HIV reservoir in the CNS of virally suppressed PWH. ANN NEUROL 2022;92:532-544.
Databáze: OpenAIRE