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T cell derived HIV-1 is present in the CSF in the face of suppressive antiretroviral therapy.

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cam.issuedOnline2021-09-23
dc.contributor.authorLustig, Gila
dc.contributor.authorCele, Sandile
dc.contributor.authorKarim, Farina
dc.contributor.authorDerache, Anne
dc.contributor.authorNgoepe, Abigail
dc.contributor.authorKhan, Khadija
dc.contributor.authorGosnell, Bernadett I
dc.contributor.authorMoosa, Mahomed-Yunus S
dc.contributor.authorNtshuba, Ntombi
dc.contributor.authorMarais, Suzaan
dc.contributor.authorJeena, Prakash M
dc.contributor.authorGovender, Katya
dc.contributor.authorAdamson, John
dc.contributor.authorKløverpris, Henrik
dc.contributor.authorGupta, Ravindra K
dc.contributor.authorHarrichandparsad, Rohen
dc.contributor.authorPatel, Vinod B
dc.contributor.authorSigal, Alex
dc.contributor.orcidLustig, Gila [0000-0002-8204-0182]
dc.contributor.orcidCele, Sandile [0000-0002-0905-7164]
dc.contributor.orcidKarim, Farina [0000-0001-9698-016X]
dc.contributor.orcidMoosa, Mahomed-Yunus S [0000-0001-6191-4023]
dc.contributor.orcidGovender, Katya [0000-0001-5753-0107]
dc.contributor.orcidGupta, Ravindra K [0000-0001-9751-1808]
dc.contributor.orcidHarrichandparsad, Rohen [0000-0002-0391-8496]
dc.contributor.orcidSigal, Alex [0000-0001-8571-2004]
dc.date.accessioned2021-11-10T00:30:19Z
dc.date.available2021-11-10T00:30:19Z
dc.date.issued2021-09
dc.description.abstractHIV cerebrospinal fluid (CSF) escape, where HIV is suppressed in blood but detectable in CSF, occurs when HIV persists in the CNS despite antiretroviral therapy (ART). To determine the virus producing cell type and whether lowered CSF ART levels are responsible for CSF escape, we collected blood and CSF from 156 neurosymptomatic participants from Durban, South Africa. We observed that 28% of participants with an undetectable HIV blood viral load showed CSF escape. We detected host cell surface markers on the HIV envelope to determine the cellular source of HIV in participants on the first line regimen of efavirenz, emtricitabine, and tenofovir. We confirmed CD26 as a marker which could differentiate between T cells and macrophages and microglia, and quantified CD26 levels on the virion surface, comparing the result to virus from in vitro infected T cells or macrophages. The measured CD26 level was consistent with the presence of T cell produced virus. We found no significant differences in ART concentrations between CSF escape and fully suppressed individuals in CSF or blood, and did not observe a clear association with drug resistance mutations in CSF virus which would allow HIV to replicate. Hence, CSF HIV in the face of ART may at least partly originate in CD4+ T cell populations.
dc.format.mediumElectronic-eCollection
dc.identifier.doi10.17863/CAM.77955
dc.identifier.eissn1553-7374
dc.identifier.issn1553-7366
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330512
dc.languageeng
dc.language.isoeng
dc.publisherPublic Library of Science (PLoS)
dc.publisher.urlhttp://dx.doi.org/10.1371/journal.ppat.1009871
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAdult
dc.subjectAlkynes
dc.subjectAnti-HIV Agents
dc.subjectBenzoxazines
dc.subjectCyclopropanes
dc.subjectEmtricitabine
dc.subjectFemale
dc.subjectHIV Infections
dc.subjectHIV-1
dc.subjectHumans
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectT-Lymphocytes
dc.subjectTenofovir
dc.titleT cell derived HIV-1 is present in the CSF in the face of suppressive antiretroviral therapy.
dc.typeArticle
dcterms.dateAccepted2021-08-06
prism.issueIdentifier9
prism.publicationDate2021
prism.publicationNamePLoS Pathog
prism.startingPagee1009871
prism.volume17
rioxxterms.licenseref.startdate2021-09-23
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1371/journal.ppat.1009871

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