Publications & Reports

Intact HIV proviruses persist in the brain despite viral suppression with ART.

Cochrane CR, Angelovich TA, Byrnes SJ, Waring E, Guanizo AC, Trollope GS, Zhou J, Vue J, Senior L, Wanicek E, Jamal Eddine J, Gartner MJ, Jenkins TA, Gorry PR, Brew BJ, Lewin SR, Estes JD, Roche M, Churchill MJ
Emerging Infections Program, School of Health and Biomedical Sciences, RMIT University; Melbourne, Australia.

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 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 PCR (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/10(6) cells), reflecting a stable CNS reservoir of HIV that persists despite therapy. Furthermore, 8/10 viremic and 6/9 virally suppressed PWH also harbored intact proviruses in the CNS (4.63 vs 12.7 intact copies/10(6) 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.

Link to publisher’s web site

Publication

  • Journal: Annals of Neurology
  • Published: 22/07/2022
  • Volume: Epub ahead of print