Dataset Information

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

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 pol or the IPDA, respectively, through use of droplet digital polymerase chain reaction (ddPCR). HIV-seronegative individuals were included as controls (n = 6).

Results

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/10⁶ cells), reflecting a stable CNS reservoir of HIV that persists despite therapy. Furthermore, 8 of 10 viremic and 6 of 9 virally suppressed PWH also harbored intact proviruses in the CNS (4.63 vs 12.7 intact copies/10⁶ cells). Viral reservoirs in CNS and matched lymphoid tissue were similar in the composition of intact and/or defective proviruses, albeit at lower levels in the brain. Importantly, CNS resident CD68+ myeloid cells in virally suppressed individuals harbored HIV DNA, directly showing the presence of a CNS resident HIV reservoir.

Interpretation

Our 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.

SUBMITTER: Cochrane CR

PROVIDER: S-EPMC9489665 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Cochrane Catherine R CR Angelovich Thomas A TA Byrnes Sarah J SJ Waring Emily E Guanizo Aleks C AC Trollope Gemma S GS Zhou Jingling J Vue Judith J Senior Lachlan L Wanicek Emma E Eddine Janna Jamal JJ Gartner Matthew J MJ Jenkins Trisha A TA Gorry Paul R PR Brew Bruce J BJ Lewin Sharon R SR Estes Jacob D JD Roche Michael M Churchill Melissa J MJ

Annals of neurology 20220809 4

<h4>Objective</h4>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).<h4>Methods</h4>Total, int ...[more]

PMID: 35867351

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Dataset Information

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

Objective

Methods

Results

Interpretation

Publications

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

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