| Baseline susceptibility of primary HIV-2 to entry inhibitors. | |
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MedLine Citation:
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PMID: 22293827 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND: 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. |
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Authors:
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Pedro Borrego; Rita Calado; José M Marcelino; Inês Bártolo; Cheila Rocha; Patrícia Cavaco-Silva; Manuela Doroana; Francisco Antunes; Fernando Maltez; Umbelina Caixas; Helena Barroso; Nuno Taveira |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-25 |
Journal Detail:
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Title: Antiviral therapy Volume: - ISSN: 2040-2058 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-2-1 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9815705 Medline TA: Antivir Ther Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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URIA-CPM, Faculdade de Farmácia de Lisboa, Lisbon, Portugal. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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