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    Por favor, use este identificador para citar o enlazar este ítem:http://uvadoc.uva.es/handle/10324/45360

    Título
    Drug resistance mutations in HIV-2 patients failing raltegravir and influence on dolutegravir response
    Autor
    Requena, Silvia
    Treviño, Ana
    Cabezas, Teresa
    Garcia Delgado, Rosa
    Amengual, María José
    Lozano, Ana Belén
    Peñaranda, María
    Fernández, Juan Manuel
    Soriano, Vicente
    Mendoza, Carmen de
    Eiros Bouza, José MaríaAutoridad UVA Orcid
    Año del Documento
    2017
    Editorial
    Oxford University Press
    Descripción
    Producción Científica
    Documento Fuente
    Journal of Antimicrobial Chemotherapy,2017, vol. 72, n. 7, p. 2083-2088
    Resumen
    Background: A broader extent of amino acid substitutions in the integrase of HIV-2 compared with HIV-1 might enable greater cross-resistance between raltegravir and dolutegravir in HIV-2 infection. Few studies have examined the virological response to dolutegravir in HIV-2 patients that failed raltegravir. Methods: All patients recorded in the HIV-2 Spanish cohort were examined. The integrase coding region was sequenced in viraemic patients. Changes associated with resistance to raltegravir and dolutegravir in HIV-1 were recorded. Results: From 319 HIV-2-infected patients recorded in the HIV-2 Spanish cohort, 53 integrase sequences from 30 individuals were obtained (20 raltegravir naive and 10 raltegravir experienced). Only one secondary mutation (E138A) was found in one of the 20 raltegravir-naive HIV-2 patients. For raltegravir-experienced individuals, the resistance mutation profile in 9 of 10 viraemic patients was as follows: N155H + A153G/S (four); Y143G + A153S (two); Q148R + G140A/S (two); and Y143C + Q91R (one). Of note, all patients with Y143G and N155H developed a rare non-polymorphic mutation at codon 153. Rescue therapy with dolutegravir was given to 5 of these 10 patients. After >6 months on dolutegravir therapy, three patients with baseline N155H experienced viral rebound. In two of them N155H was replaced by Q148K/R and in another by G118R. Conclusions: A wide repertoire of resistance mutations in the integrase gene occur in HIV-2-infected patients failing on raltegravir. Although dolutegravir may allow successful rescue in most HIV-2 raltegravir failures, we report and characterize three cases of dolutegravir resistance in HIV-2 patients, emerging variants Q148K and Q148R and a novel change G118R.
    Materias Unesco
    32 Ciencias Médicas
    Palabras Clave
    VIH
    Mutación
    Raltegravir
    Dolutegravir
    ISSN
    0305-7453
    Revisión por pares
    SI
    DOI
    10.1093/jac/dkx090
    Patrocinador
    Fondo de Investigación Sanitaria-Fondos FEDER (FIS, PI13/01574; ICI14/0274, CES12/003, FI14/00264, CD14/00243)
    Version del Editor
    https://academic.oup.com/jac/article/72/7/2083/3078891
    Propietario de los Derechos
    © Oxford University Press
    Idioma
    eng
    URI
    http://uvadoc.uva.es/handle/10324/45360
    Tipo de versión
    info:eu-repo/semantics/publishedVersion
    Derechos
    openAccess
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    • GIV - Artículos de Revista [46]
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