Impact of genotypic diversity on selection of subtype-specific drug resistance profiles during raltegravir-based therapy in individuals infected with B and BF recombinant HIV-1 strains.

Autor:	Sánchez D; Laboratorio de Biología Celular y Retrovirus-CONICET, Unidad de Virología y Epidemiología Molecular, Hospital de Pediatría 'Juan P. Garrahan', Buenos Aires, Argentina.; Centro Provincial VIH/SIDA y Hepatitis Virales de la Provincia de Buenos Aires, Instituto Biológico Dr Tomás Perón, La Plata, Argentina., Arazi Caillaud S; Servicio de Epidemiología e Infectología, Hospital de Pediatría 'Juan P. Garrahan', Buenos Aires, Argentina., Zapiola I; Unidad de Virología, Hospital de Infecciosas 'Francisco J. Muñiz', Buenos Aires, Argentina., Fernandez Giuliano S; Unidad de Virología, Hospital de Infecciosas 'Francisco J. Muñiz', Buenos Aires, Argentina., Bologna R; Servicio de Epidemiología e Infectología, Hospital de Pediatría 'Juan P. Garrahan', Buenos Aires, Argentina., Mangano A; Laboratorio de Biología Celular y Retrovirus-CONICET, Unidad de Virología y Epidemiología Molecular, Hospital de Pediatría 'Juan P. Garrahan', Buenos Aires, Argentina., Aulicino PC; Laboratorio de Biología Celular y Retrovirus-CONICET, Unidad de Virología y Epidemiología Molecular, Hospital de Pediatría 'Juan P. Garrahan', Buenos Aires, Argentina.
Jazyk:	angličtina
Zdroj:	The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2020 Jun 01; Vol. 75 (6), pp. 1567-1574.
DOI:	10.1093/jac/dkaa042
Abstrakt:	Background: Current knowledge on HIV-1 resistance to integrase inhibitors (INIs) is based mostly on subtype B strains. This contrasts with the increasing use of INIs in low- and middle-income countries, where non-B subtypes predominate. Materials and Methods: HIV-1 drug resistance genotyping was performed in 30 HIV-1-infected individuals undergoing virological failure to raltegravir. Drug resistance mutations (DRMs) and HIV-1 subtype were characterized using Stanford HIVdb and phylogenetic analyses. Results: Of the 30 integrase (IN) sequences, 14 were characterized as subtype F (47%), 8 as subtype B (27%), 7 as BF recombinants (23%) and 1 as a putative CRF05_DF (3%). In 25 cases (83%), protease and reverse transcriptase (PR-RT) sequences from the same individuals confirmed the presence of different BF recombinants. Stanford HIVdb genotyping was concordant with phylogenetic inference in 70% of IN and 60% of PR-RT sequences. INI DRMs differed between B and F IN subtypes, with Q148K/R/H, G140S and E138K/A being more prevalent in subtype B (63% versus 0%, P = 0.0021; 50% versus 0%, P = 0.0096; and 50% versus 0%, P = 0.0096, respectively). These differences were independent of the time on raltegravir therapy or viral load at the time of genotyping. INI DRMs in subtype F IN genomes predicted a lower level of resistance to raltegravir and no cross-resistance to second-generation INIs. Conclusions: Alternative resistance pathways to raltegravir develop in subtypes B and F IN genomes, with implications for clinical practice. Evaluating the role of HIV-1 subtype in development and persistence of mutations that confer resistance to INIs will be important to improve algorithms for resistance testing and optimize the use of INIs. (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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