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Dynamics of HIV Reservoir and HIV-1 Viral Splicing in HCV-Exposed Individuals after Elimination with DAAs or Spontaneous Clearance

2022-06-21Journal article Open access
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dc.contributor.authorMartínez-Román, Paula
dc.contributor.authorCrespo-Bermejo, Celia
dc.contributor.authorValle-Millares, Daniel
dc.contributor.authorLara Aguilar, Violeta
dc.contributor.authorArca-Lafuente, Sonia
dc.contributor.authorMartín-Carbonero, Luz
dc.contributor.authorRyan, Pablo
dc.contributor.authorGil, Ignacio De Los Santos
dc.contributor.authorLópez-Huertas, María Rosa
dc.contributor.authorPalladino, Claudia
dc.contributor.authorMuñoz-Muñoz, María
dc.contributor.authorFernández Rodríguez, Amanda
dc.contributor.authorCoiras, Mayte
dc.contributor.authorBriz, Verónica
dc.contributor.authorCOVIHEP network
dc.date.accessioned2023-08-31T14:16:18Z
dc.date.available2023-08-31T14:16:18Z
dc.date.issued2022-06-21
dc.date.updated2023-02-09T12:15:21Z
dc.description.abstractBackground: Although human immunodeficiency virus type 1 (HIV-1) reservoir size is very stable under antiretroviral therapy (ART), individuals exposed to the Hepatitis C virus (HCV) (chronically coinfected and spontaneous clarifiers) show an increase in HIV reservoir size and in spliced viral RNA, which could indicate that the viral protein regulator Tat is being more actively synthesized and, thus, could lead to a higher yield of new HIV. However, it is still unknown whether the effect of HCV elimination with direct-acting antivirals (DAAs) could modify the HIV reservoir and splicing. Methods: This longitudinal study (48 weeks’ follow-up after sustained virological response) involves 22 HIV+-monoinfected individuals, 17 HIV+/HCV- spontaneous clarifiers, and 24 HIV+/HCV+ chronically infected subjects who eliminated HCV with DAAs (all of them aviremic, viral load < 50). Viral-spliced RNA transcripts and proviral DNA copies were quantified by qPCR. Paired samples were analyzed using a mixed generalized linear model. Results: A decrease in HIV proviral DNA was observed in HIV+/HCV- subjects, but no significant differences were found for the other study groups. An increased production of multiple spliced transcripts was found in HIV+ and HIV+/HCV+ individuals. Conclusions: We conclude that elimination of HCV by DAAs was unable to revert the consequences derived from chronic HCV infection for the reservoir size and viral splicing, which could indicate an increased risk of rapid HIV-reservoir reactivation. Moreover, spontaneous clarifiers showed a significant decrease in the HIV reservoir, likely due to an enhanced immune response in these individuals.pt_PT
dc.description.sponsorshipFinancial support was provided by the Instituto de Salud Carlos III to V.B. and A.F.-R. (PI15CIII/00031 and PI18CIII/00020) and the SPANISH AIDS Research Network (RD16CIII/0002/0001 and RD16CIII/0002/0002—ISCIII—FEDER). A.F.-R. is supported by the Miguel Servet program from Fondo de Investigación Sanitaria (ISCIII) (CP14/CIII/00010). Financial support was provided by the National Institutes of Health (NIH) (Grant R01AI143567) for M.C. The work of M.R.L.-H. is financed by the NIH (Grant R01AI143567). C.P. is funded by FCT—Fundação para a Ciência e a Tecnologia, I.P. (national funding), under a contract program as defined by DL No. 57/2016 and Law No. 57/2017.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMartínez-Román P, Crespo-Bermejo C, Valle-Millares D, Lara-Aguilar V, Arca-Lafuente S, Martín-Carbonero L, et al. Dynamics of HIV Reservoir and HIV-1 Viral Splicing in HCV-Exposed Individuals after Elimination with DAAs or Spontaneous Clearance. Journal of Clinical Medicine [Internet]. 2022 Jun 21;11(13):3579. Available from: http://dx.doi.org/10.3390/jcm11133579pt_PT
dc.identifier.doi10.3390/jcm11133579pt_PT
dc.identifier.issn2077-0383
dc.identifier.slugcv-prod-3138357
dc.identifier.urihttp://hdl.handle.net/10451/59108
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relation.publisherversionhttps://www.mdpi.com/2077-0383/11/13/3579pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectHIV/HCVpt_PT
dc.subjectHIV reservoirpt_PT
dc.subjectviral splicingpt_PT
dc.subjectdynamicspt_PT
dc.subjectcoinfectionpt_PT
dc.subjectDAAspt_PT
dc.subjectspontaneous HCV clearancept_PT
dc.titleDynamics of HIV Reservoir and HIV-1 Viral Splicing in HCV-Exposed Individuals after Elimination with DAAs or Spontaneous Clearancept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage3594pt_PT
oaire.citation.issue13pt_PT
oaire.citation.startPage3579pt_PT
oaire.citation.titleJournal of Clinical Medicinept_PT
oaire.citation.volume11pt_PT
person.familyNameLara Aguilar
person.familyNameArca de Lafuente
person.familyNameMARTÍN CARBONERO
person.familyNameRyan
person.familyNameDe Los Santos Gil
person.familyNamePalladino
person.familyNameFernández Rodríguez
person.familyNameCoiras
person.familyNameBriz
person.givenNameVioleta
person.givenNameSonia
person.givenNameLUZ
person.givenNamePablo
person.givenNameIgnacio
person.givenNameClaudia
person.givenNameAmanda
person.givenNameMayte
person.givenNameVerónica
person.identifier2933883
person.identifier2437626
person.identifier2298943
person.identifier2730269
person.identifier.ciencia-id721D-6851-20D5
person.identifier.orcid0000-0003-0015-5961
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person.identifier.orcid0000-0001-8102-4079
person.identifier.orcid0000-0002-4212-7419
person.identifier.orcid0000-0001-7073-5211
person.identifier.orcid0000-0002-8148-0928
person.identifier.orcid0000-0002-5110-2213
person.identifier.orcid0000-0001-6464-5770
person.identifier.orcid0000-0003-2297-5098
person.identifier.ridA-7807-2019
person.identifier.ridAAM-1924-2021
person.identifier.ridT-4183-2017
person.identifier.scopus-author-id57210940011
person.identifier.scopus-author-id26432219100
person.identifier.scopus-author-id7102671715
person.identifier.scopus-author-id20336977900
person.identifier.scopus-author-id9332849600
rcaap.cv.cienciaid721D-6851-20D5 | Claudia Palladino
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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