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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

2019Journal article Open access
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dc.contributor.authorBártolo, I
dc.contributor.authorBorrego, P
dc.contributor.authorGomes, P
dc.contributor.authorGonçalves, F
dc.contributor.authorCaixas, U
dc.contributor.authorPinto, IV
dc.contributor.authorTaveira, N
dc.date.accessioned2020-05-15T14:25:32Z
dc.date.available2020-05-15T14:25:32Z
dc.date.issued2019
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.pt_PT
dc.identifier.doi10.1016/j.antiviral.2018.10.018pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.17/3444
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.subjectAdeninept_PT
dc.subjectAnti-HIV Agentspt_PT
dc.subjectDrug Discoverypt_PT
dc.subjectHIV-2pt_PT
dc.subjectHumanspt_PT
dc.subjectMicrobial Sensitivity Testspt_PT
dc.subjectMutationpt_PT
dc.subjectReverse Transcriptase Inhibitorspt_PT
dc.subjectVirus Replicationpt_PT
dc.subjectDrug Resistance, Multiple, Viralpt_PT
dc.subjectHSJ MEDpt_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.citation.endPage89pt_PT
oaire.citation.startPage85pt_PT
oaire.citation.titleAntiviral researchpt_PT
oaire.citation.volume161pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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