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Baseline Susceptibility of Primary HIV-2 to Entry Inhibitors

2012Journal article Open access
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dc.contributor.authorBorrego, P
dc.contributor.authorCalado, R
dc.contributor.authorMarcelino, JM
dc.contributor.authorBártolo, I
dc.contributor.authorRocha, C
dc.contributor.authorCavaco-Silva, P
dc.contributor.authorDoroana, M
dc.contributor.authorAntunes, F
dc.contributor.authorMaltez, F
dc.contributor.authorCaixas, U
dc.contributor.authorBarroso, H
dc.contributor.authorTaveira, N
dc.date.accessioned2016-03-09T16:46:00Z
dc.date.available2016-03-09T16:46:00Z
dc.date.issued2012
dc.description.abstractBACKGROUND: The baseline susceptibility of primary HIV-2 to maraviroc (MVC) and other entry inhibitors is currently unknown. METHODS: 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 cell-based assay. The 50% inhibitory concentration (IC(50)), 90% inhibitory concentration (IC(90)) and dose-response curve slopes were determined for each drug. RESULTS: ENF and T-1249 were significantly less active on 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 IC(50) and IC(90) values. MVC, however, inhibited the replication of R5 HIV-2 variants with significantly higher IC(90) 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. CONCLUSIONS: 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.pt_PT
dc.identifier.citationAntivir Ther. 2012;17(3):565-70pt_PT
dc.identifier.doi10.3851/IMP1996pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.17/2417
dc.language.isoengpt_PT
dc.publisherInternational Medical Presspt_PT
dc.subjectHSJ MEDpt_PT
dc.subjectHCC INFpt_PT
dc.subjectAmides/pharmacologypt_PT
dc.subjectAmides/therapeutic usept_PT
dc.subjectAnti-HIV Agents/pharmacologypt_PT
dc.subjectAnti-HIV Agents/therapeutic usept_PT
dc.subjectCCR5 Receptor Antagonistspt_PT
dc.subjectCyclohexanes/pharmacologypt_PT
dc.subjectCyclohexanes/therapeutic usept_PT
dc.subjectHIV Envelope Protein gp41/pharmacologypt_PT
dc.subjectHIV Envelope Protein gp41/therapeutic usept_PT
dc.subjectHIV Fusion Inhibitors/pharmacologypt_PT
dc.subjectHIV Fusion Inhibitors/therapeutic usept_PT
dc.subjectHIV Infections/drug therapypt_PT
dc.subjectHIV Infections/virologypt_PT
dc.subjectHIV-1/drug effectspt_PT
dc.subjectHIV-2/drug effectspt_PT
dc.subjectInhibitory Concentration 50pt_PT
dc.subjectMicrobial Sensitivity Testspt_PT
dc.subjectPeptide Fragments/pharmacologypt_PT
dc.subjectPeptide Fragments/therapeutic usept_PT
dc.subjectQuaternary Ammonium Compounds/pharmacologypt_PT
dc.subjectQuaternary Ammonium Compounds/therapeutic usept_PT
dc.subjectTriazoles/pharmacologypt_PT
dc.subjectTriazoles/therapeutic usept_PT
dc.titleBaseline Susceptibility of Primary HIV-2 to Entry Inhibitorspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage570pt_PT
oaire.citation.startPage565pt_PT
oaire.citation.titleAntiviral Therapypt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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