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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

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dc.contributor.authorBártolo, Inês
dc.contributor.authorBorrego, Pedro
dc.contributor.authorGomes, Perpetua
dc.contributor.authorGonçalves, Maria Fátima
dc.contributor.authorCaixas, Umbelina
dc.contributor.authorVaz-Pinto, Inês
dc.contributor.authorTaveira, Nuno
dc.date.accessioned2023-08-23T13:36:09Z
dc.date.available2023-08-23T13:36:09Z
dc.date.issued2019
dc.date.updated2023-02-03T14:09:32Z
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.sponsorshipFinancial support for this research was provided by the Fundação para a Ciência e a Tecnologia (FCT), Portugal (project VIH/SAU/0029/2011) and by the LIFE project of the European and Developing Countries Clinical Trials Partnership (EDCTP) program supported by the European Union. Inês Bártolo is supported by a post-doc fellowship (SFRH/BPD/76225/2011) from Fundação para a Ciência e a Tecnologia (FCT).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBártolo I, Borrego P, Gomes P, Gonçalves F, Caixas U, Pinto IV, et al. 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. Antiviral Research [Internet]. 1 de janeiro de 2019;161:85–9. Disponível em: https://www.sciencedirect.com/science/article/pii/S0166354218305424pt_PT
dc.identifier.doi10.1016/j.antiviral.2018.10.018pt_PT
dc.identifier.eid2-s2.0-85057042987
dc.identifier.slugcv-prod-1108448
dc.identifier.urihttp://hdl.handle.net/10451/58974
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationDESENVOLVIMENTO DE NOVOS MICROBICIDAS PARA PREVENIR A INFECÇÃO POR VIH
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/abs/pii/S0166354218305424pt_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
person.familyNameBártolo
person.familyNameBorrego
person.familyNameRodrigues Gomes Cavaco Silva
person.familyNameGonçalves
person.familyNameCaixas
person.familyNameVaz-Pinto
person.familyNameTaveira
person.givenNameInês
person.givenNamePedro
person.givenNamePerpétua da Conceição
person.givenNameMaria Fátima
person.givenNameUmbelina
person.givenNameInês
person.givenNameNuno
person.identifier.ciencia-id661E-F5CB-F85A
person.identifier.ciencia-idA71C-0177-722F
person.identifier.ciencia-id7219-B8D3-2942
person.identifier.ciencia-id7111-3383-A926
person.identifier.orcid0000-0002-2022-8921
person.identifier.orcid0000-0002-1949-9484
person.identifier.orcid0000-0003-3271-8255
person.identifier.orcid0000-0002-2124-5811
person.identifier.orcid0000-0002-0538-2146
person.identifier.orcid0000-0002-6281-8591
person.identifier.orcid0000-0003-0176-5585
person.identifier.ridH-6968-2013
person.identifier.scopus-author-id25225039400
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.cv.cienciaid661E-F5CB-F85A | Inês Bártolo
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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