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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Drug resistance mutations in HIV-2 patients failing raltegravir and influence on dolutegravir response
Journal of Antimicrobial Chemotherapy, Volume 72, No. 7, Year 2017
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Description
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 > 6months 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. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
Authors & Co-Authors
Soriano, Vicente Vicente
Spain, Madrid
Universidad Autónoma de Madrid
Spain, Madrid
Hospital Universitario la Paz
de-Mendoza, Carmen
Spain, Majadahonda
Hospital Universitario Puerta de Hierro Majadahonda
Rodríguez, Carmen
Unknown Affiliation
del Romero, Jorge D.
Unknown Affiliation
Aguilera, Antonio
Unknown Affiliation
Benito, R.
Spain, Zaragoza
Hospital Clinico Universitario Lozano Blesa
Algarate, S.
Spain, Zaragoza
Hospital Clinico Universitario Lozano Blesa
Ortiz de Lejarazu, Raúl O.
Spain, Valladolid
Hospital Clínico Universitario de Valladolid
Eiros-Bouza, José María
Spain, Valladolid
Hospital Universitario Río Hortega
Manzardo, Christian
Spain, Barcelona
Institut D'investigacions Biomèdiques August pi I Sunyer - Idibaps
Miró, José María
Spain, Barcelona
Institut D'investigacions Biomèdiques August pi I Sunyer - Idibaps
García, Juan González
Unknown Affiliation
Calderón, Enrique J.
Spain, Madrid
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
Iglesias, M. A.R.
Spain, Cadiz
Hospital Universitario Puerta Del Mar
Ramos-Rincón, José Manuel
Spain, Alicante
Hospital General Universitario de Alicante
Gutieŕrez, Félix
Unknown Affiliation
Cilla, Gustavo
Spain, Donostia-san Sebastian
Osakidetza, Donostia University Hospital
Pérez-Trallero, Emilio
Spain, Donostia-san Sebastian
Osakidetza, Donostia University Hospital
Montejo, Jose M.
Spain, Baracaldo
Osakidetza, Cruces University Hospital
Górgolas, Miguel
Spain, Madrid
Fundación Jiménez Díaz
García, Federico Alcacer
Spain, Granada
Hospital Universitario San Cecilio
Barreiro, Pablo M.
Spain, Madrid
Hospital Universitario la Paz
Statistics
Citations: 21
Authors: 22
Affiliations: 37
Identifiers
Doi:
10.1093/jac/dkx090
ISSN:
03057453
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases
Study Design
Cohort Study