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Epigenetic age acceleration changes 2 years after antiretroviral therapy initiation in adults with HIV: a substudy of the NEAT001/ANRS143 randomised trial

dc.rights.licenseopenen_US
dc.contributor.authorESTEBAN-CANTOS, Andres
dc.contributor.authorRODRIGUEZ-CENTENO, Javier
dc.contributor.authorBARRUZ, Pilar
dc.contributor.authorALEJOS, Belen
dc.contributor.authorSAIZ-MEDRANO, Gabriel
dc.contributor.authorNEVADO, Julian
dc.contributor.authorMARTIN, Artur
dc.contributor.authorGAYA, Francesco
dc.contributor.authorDE MIGUEL, Rosa
dc.contributor.authorBERNARDINO, Jose I.
dc.contributor.authorMONTEJANO, Rocio
dc.contributor.authorMENA-GARAY, Beatriz
dc.contributor.authorCADINANOS, Julen
dc.contributor.authorFLORENCE, Eric
dc.contributor.authorMULCAHY, Fiona
dc.contributor.authorBANHEGYI, Denes
dc.contributor.authorANTINORI, Andrea
dc.contributor.authorPOZNIAK, Anton
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorWALLET, Cedrick
dc.contributor.authorRAFFI, Francois
dc.contributor.authorRODES, Berta
dc.contributor.authorARRIBAS, Jose R.
dc.date.accessioned2021-06-24T09:22:33Z
dc.date.available2021-06-24T09:22:33Z
dc.date.issued2021-04
dc.identifier.issn2352-3018en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/79286
dc.description.abstractEnBACKGROUND: DNA methylation-based estimators of biological age are reliable biomarkers of the ageing process. We aimed to investigate a range of epigenetic ageing biomarkers in a substudy of the NEAT001/ANRS143 clinical trial, which compared ritonavir-boosted darunavir with either raltegravir or tenofovir disoproxil fumarate and emtricitabine in antiretroviral therapy (ART)-naive adults. METHODS: We analysed frozen whole blood samples from 168 ART-naive participants with HIV from the NEAT001/ANRS143 trial, before ART initiation and after 2 years of ART (84 participants on ritonavir-boosted darunavir with raltegravir and 84 participants on ritonavir-boosted darunavir with tenofovir disoproxil fumarate and emtricitabine). We also included 44 participants without HIV with a similar age and sex distribution. We analysed DNA methylation. Epigenetic age estimators (Horvath's clock, Hannum's clock, GrimAge, and PhenoAge) and estimated leucocyte compositions were generated using Horvath's New Online Methylation Age Calculator and Houseman's method. We calculated epigenetic age acceleration measures for each estimator of epigenetic age. The NEAT001/ANRS143 trial is registered with ClinicalTrials.gov, NCT01066962. FINDINGS: Compared with the HIV-uninfected group, ART-naive participants with HIV showed higher epigenetic age acceleration (EAA) according to all EAA estimators (mean 2·5 years, 95% CI 1·89-3·22 for Horvath-EAA; 1·4 years, 0·74-1·99 for Hannum-EAA; 2·8 years, 1·97-3·68 for GrimAge-EAA; and 7·3 years, 6·40-8·13 for PhenoAge-EAA), with all differences being statistically significant except for Hannum-EAA (Horvath-EAA p=0·0008; Hannum-EAA p=0·059; GrimAge-EAA p=0·0021; and PhenoAge-EAA p<0·0001). Epigenetic ageing was more pronounced in participants who had CD4 counts less than 200 cells per μL (significant for PhenoAge and Hannum's clock, p=0·0015 and p=0·034, respectively) or viral loads over 100 000 copies per mL at baseline (significant for PhenoAge, p=0·017). After 2 years of ART, epigenetic age acceleration was reduced, although PhenoAge and GrimAge remained significantly higher in participants with HIV compared with participants without HIV (mean difference 3·69 years, 95% CI 1·77-5·61; p=0·0002 and 2·2 years, 0·47-3·99; p=0·013, respectively). There were no significant differences in the ART effect on epigenetic ageing between treatment regimens. At baseline, participants with HIV showed dysregulation of DNA methylation-based estimated leucocyte subsets towards more differentiated T-cell phenotypes and proinflammatory leucocytes, which was also partly restored with ART. INTERPRETATION: ART initiation partly reversed epigenetic ageing associated with untreated HIV infection. Further studies are needed to understand the long-term dynamics and clinical relevance of epigenetic ageing biomarkers in people with HIV. FUNDING: NEAT-ID Foundation.
dc.language.isoENen_US
dc.title.enEpigenetic age acceleration changes 2 years after antiretroviral therapy initiation in adults with HIV: a substudy of the NEAT001/ANRS143 randomised trial
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/s2352-3018(21)00006-0en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
bordeaux.journalLancet HIVen_US
bordeaux.pagee197-e205en_US
bordeaux.volume8en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue4en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamCMGen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03269699
hal.version1
hal.date.transferred2021-06-24T09:22:41Z
hal.exporttrue
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