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Ultrasensitive detection of p24 in plasma samples from people with primary and chronic HIV-1 infection

dc.rights.licenseopenen_US
dc.contributor.authorPASSAES, Caroline
dc.contributor.authorDELAGREVERIE, Heloise M.
dc.contributor.authorAVETTAND-FENOEL, Veronique
dc.contributor.authorDAVID, Annie
dc.contributor.authorMONCEAUX, Valerie
dc.contributor.authorESSAT, Asma
dc.contributor.authorMULLER-TRUTWIN, Michaela
dc.contributor.authorDUFFY, Darragh
dc.contributor.authorDE CASTRO, Nathalia
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorWITTKOP, Linda
dc.contributor.authorROUZIOUX, Christine
dc.contributor.authorMOLINA, Jean-Michel
dc.contributor.authorMEYER, Laurence
dc.contributor.authorDELAUGERRE, Constance
dc.contributor.authorSAEZ-CIRION, Asier
dc.date.accessioned2021-07-08T10:04:31Z
dc.date.available2021-07-08T10:04:31Z
dc.date.issued2021-05-05
dc.identifier.issn0022-538xen_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/100649
dc.description.abstractEnHIV-1 Gag p24 has long been identified as an informative biomarker of HIV replication, disease progression and therapeutic efficacy, but the lower sensitivity of immunoassays in comparison to molecular tests and the interference with antibodies in chronic HIV infection limits its application for clinical monitoring. The development of ultrasensitive protein detection technologies may help overcoming these limitations. Here we evaluated whether immune-complex dissociation combined with ultrasensitive digital ELISA Simoa technology could be used to quantify p24 in plasma samples from people with HIV-1 infection. We found that, among different immune-complex dissociation methods, only acid-mediated dissociation was compatible with ultrasensitive p24 quantification by digital ELISA, strongly enhancing p24 detection at different stages of HIV-1 infection. We show that ultrasensitive p24 levels correlated positively with plasma HIV-RNA and HIV-DNA and negatively with CD4+ T cells in the samples from people with primary and chronic HIV-1 infection. In addition, p24 levels also correlated with plasma D-dimers and IFNα levels. P24 levels sharply decreased to undetectable levels after initiation of combined antiretroviral treatment (cART). However, we identified a group of people who, 48 weeks after cART initiation, had detectable p24 levels despite most having undetectable viral loads. These people had different virologic and immunologic baseline characteristics when compared with people who had undetectable p24 after cART. These results demonstrate that ultrasensitive p24 analysis provides an efficient and robust mean to monitor p24 antigen in plasma samples from people with HIV-1 infection, including during antiretroviral treatment, and may provide complementary information to other commonly used biomarkers.ImportanceThe introduction of combined antiretroviral treatment has transformed HIV-1 infection in a manageable condition. In this context, there is a need for additional biomarkers to monitor HIV-1 residual disease or the outcome of new interventions, such as in the case of HIV cure strategies. The p24 antigen has a long half-life outside viral particles and it is therefore a very promising marker to monitor episodes of viral replication or transient activation of the viral reservoir. However, the formation of immune-complexes with anti-p24 antibodies makes its quantification difficult beyond acute HIV-1 infection. We show here that, upon immune-complex dissociation, new technologies allow the ultrasensitive p24 quantification in plasma samples throughout HIV-1 infection, at levels close to that of viral RNA and DNA determinations. Our results further indicate that ultrasensitive p24 quantification may have added value when used in combination with other classic clinical biomarkers.
dc.language.isoENen_US
dc.subject.enHIV/AIDS
dc.subject.enHIV p24 antigen
dc.subject.enGag p24
dc.subject.enSimoa
dc.subject.enELISA
dc.subject.enBiomarker
dc.subject.enPlasma
dc.subject.enPlasma marker
dc.title.enUltrasensitive detection of p24 in plasma samples from people with primary and chronic HIV-1 infection
dc.typeArticle de revueen_US
dc.identifier.doi10.1128/jvi.00016-21en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed33952636en_US
bordeaux.journalJournal of Virologyen_US
bordeaux.volume95en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue14en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamMORPH3Eusen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.exportfalse
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