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Baseline susceptibility of primary HIV-2 to entry inhibitors

dc.contributor.authorBorrego, Pedro
dc.contributor.authorCalado, Rita
dc.contributor.authorMarcelino, José M
dc.contributor.authorBártolo, Inês
dc.contributor.authorRocha, Cheila
dc.contributor.authorCavaco-Silva, Patrícia
dc.contributor.authorDoroana, Manuela
dc.contributor.authorAntunes, Francisco
dc.contributor.authorMaltez, Fernando
dc.contributor.authorCaixas, Umbelina
dc.contributor.authorBarroso, Helena
dc.contributor.authorTaveira, Nuno
dc.date.accessioned2013-11-29T12:35:32Z
dc.date.available2013-11-29T12:35:32Z
dc.date.issued2012-01
dc.descriptionThis is the author’s version of a work accepted for publication by International Medical Press. Changes resulting from the publishing process, including peer review, editing and formatting, might not be reflected in this document. A definitive version was published in Antiviral Therapy, 17 (3): 565-570, January © 2012 International Medical Press.
dc.description.abstractBackground: The baseline susceptibility of primary HIV-2 to maraviroc (MVC) and other entry inhibitors is currently unknown.por
dc.description.abstractMethods: The susceptibility of 19 HIV-2 isolates obtained from asymptomatic and AIDS patients and seven HIV-1 clinical isolates to the fusion inhibitors enfuvirtide (ENF) and T-1249, and to the coreceptor antagonists AMD3100, TAK-779 and MVC, was measured using a TZM-bl cellbased assay. The 50% inhibitory concentration (IC50), 90% inhibitory concentration (IC90) and dose–response curve slopes were determined for each drug.por
dc.description.abstracton HIV-2 than on HIV-1 (211- and 2-fold, respectively). AMD3100 and TAK-779 inhibited HIV-2 and HIV-1 CXCR4 tropic (X4) and CCR5 tropic (R5) variants with similar IC50 and IC90 values. MVC, however, inhibited the replication of R5 HIV-2 variants with significantly higher IC90 values (42.7 versus 9.7 nM; P<0.0001) and lower slope values (0.7 versus 1.3; P<0.0001) than HIV-1. HIV-2 R5 variants derived from AIDS patients were significantly less sensitive to MVC than variants from asymptomatic patients, this being inversely correlated with the absolute number of CD4+ T-cells.por
dc.description.abstractConclusions: T-1249 is a potent inhibitor of HIV-2 replication indicating that new fusion inhibitors might be useful to treat HIV-2 infection. Coreceptor antagonists TAK- 779 and AMD3100 are also potent inhibitors of HIV-2 replication. The reduced sensitivity of R5 variants to MVC, especially in severely immunodeficient patients, indicates that the treatment of HIV-2-infected patients with MVC might require higher dosages than those used in HIV-1 patients, and should be adjusted to the disease stage.por
dc.identifier.citationAntiviral Therapy 2012; 17:565-570 doi: 10.3851/IMP1996por
dc.identifier.issn2040-2058
dc.identifier.issn1359-6535
dc.identifier.urihttp://hdl.handle.net/10400.26/4993
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherInternational Medical Presspor
dc.relation.publisherversionhttp://www.intmedpress.com/journals/avt/abstract.cfm?id=1996&pid=88por
dc.subjectHIV-2por
dc.subjectinhibitorspor
dc.titleBaseline susceptibility of primary HIV-2 to entry inhibitorspor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage570por
oaire.citation.startPage565por
oaire.citation.titleAntiviral Therapypor
oaire.citation.volume17, n.º 3por
rcaap.rightsopenAccesspor
rcaap.typearticlepor

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