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In vitro evaluation of novel reverse transcriptase inhibitors TAF (tenofovir alafenamide) and OBP-601 (2,3-didehydro-3-deoxy-4-ethynylthymidine) against multi-drug resistant primary isolates of HIV-2

2019-01Journal article Restricted access
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dc.contributor.authorBártolo, Inês
dc.contributor.authorBorrego, Pedro
dc.contributor.authorGomes, Perpétua
dc.contributor.authorGonçalves, Fátima
dc.contributor.authorCaixas, Umbelina
dc.contributor.authorPinto, Inês V.
dc.contributor.authorTaveira, Nuno
dc.date.accessioned2019-12-20T10:44:45Z
dc.date.available2019-12-20T10:44:45Z
dc.date.issued2019-01
dc.description.abstractNew antiretroviral drugs are needed to treat HIV-2 infected patients failing therapy. Herein, we evaluate the activity of novel reverse transcriptase inhibitors tenofovir alafenamide (TAF) and OBP-601(2,3-didehydro-3-deoxy-4-ethynylthymidine) against primary isolates from HIV-2 infected patients experiencing virologic failure. TAF and OBP-601 were tested against twelve primary isolates obtained from nine drug-experienced patients failing therapy and three drug naïve patients using a single-round infectivity assay in TZM-bl cells. The RT-coding region of pol was sequenced and the GRADE algorithm was used to identify resistance profiles and mutations. TAF and OBP-601 inhibited the replication of almost all isolates at a median EC50 of 0.27 nM and 6.83 nM, respectively. Two isolates showed moderate-level resistance to OBP-601 or TAF and two other isolates showed high-level resistance to OBP-601 or to both drugs. With one exception, all resistant viruses had canonical nucleoside reverse transcriptase inhibitors (NRTIs)-associated resistance mutations (K65R, N69S, V111I, Y115F, Q151M and M184V). Our results show that TAF has potent activity against most multi-drug resistant HIV-2 isolates and should be considered for the treatment of HIV-2 infected patients failing therapy.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationAntiviral Res. 2019 Jan;161:85-89. doi: 10.1016/j.antiviral.2018.10.018.pt_PT
dc.identifier.doi10.1016/j.antiviral.2018.10.018pt_PT
dc.identifier.issn0166-3542
dc.identifier.urihttp://hdl.handle.net/10400.26/30647
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationDESENVOLVIMENTO DE NOVOS MICROBICIDAS PARA PREVENIR A INFECÇÃO POR VIH
dc.relation.publisherversionhttps://doi.org/10.1016/j.antiviral.2018.10.018pt_PT
dc.subjectHIV-2pt_PT
dc.subjectSusceptibility to TAFpt_PT
dc.subjectTDF and OBP-601pt_PT
dc.subjectResistance mutationspt_PT
dc.titleIn vitro evaluation of novel reverse transcriptase inhibitors TAF (tenofovir alafenamide) and OBP-601 (2,3-didehydro-3-deoxy-4-ethynylthymidine) against multi-drug resistant primary isolates of HIV-2pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleDESENVOLVIMENTO DE NOVOS MICROBICIDAS PARA PREVENIR A INFECÇÃO POR VIH
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/VIH%2FSAU%2F0029%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F76225%2F2011/PT
oaire.citation.endPage89pt_PT
oaire.citation.startPage85pt_PT
oaire.citation.titleAntiviral Researchpt_PT
oaire.citation.volume161pt_PT
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctPolítica de copyright do editorpt_PT
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicatione63cde82-fa32-4aed-90e7-c9443427f2e1
relation.isProjectOfPublicationc548f6e8-c9c8-4ad9-9572-d64134c3a608
relation.isProjectOfPublication.latestForDiscoverye63cde82-fa32-4aed-90e7-c9443427f2e1

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