Primary resistance to integrase strand transfer inhibitors in Spain using ultrasensitive HIV-1 genotyping
Authors: Casadellà M , Santos J R , Noguera-Julian M , Micán-Rivera R , Domingo P , Antela A , Portilla J , Sanz J , Montero-Alonso M , Navarro J , Masiá M , Valcarce-Pardeiro N , Ocampo A , Pérez-Martínez L , Pasquau J , Vivancos M J , Imaz A , Carmona-Oyaga P , Muñoz-Medina L , Villar-García J , Barrufet P , Paredes R ,   the INSTINCT Study Group, Santos José R , Bravo Isabel , Chamorro Anna , Miranda Cristina , Micán Rafael , González Juan , Antela Antonio , Diez Marcos , Portilla Irene , Carreres Melissa , Giner Livia , Boix Vicente , Reus Sergio , Merino Esperanza , Torrús Diego , Portilla Joaquín , Sanz Jesús , Liarte Ángela Gutiérrez , Berrocal Ana Gómez , Domingo Pere , del María , Gutiérrez Mar , Mateo María Gracia , Rodríguez Jèssica Muñoz , Montero-Alonso Marta , Curran Adrià , Torrella Ariadna , Planas Bibiana , Navarro Jordi , Masiá Mar , Padilla Sergio , Robledano Catalina , Adsuar Araceli , Montolio Fernando , Gutiérrez Félix , Pardeiro Nieves Valcarce , Álvarez Hortensia , Mariño Ana , Ocampo Antonio , Rodríguez Alfredo , Miralles Celia , Pérez-Martínez Laura , Blanco José Ramón , Vallecillos Coral García , Pasquau Juan , Pérez-Elías María Jésus , Dronda Fernando , Vivancos María Jesús , Moreno Santiago , Imaz Arkaitz , Podzamczer Daniel , Ibarguren Maialen , Kortajarena Xabier , Carmona María Pilar , Iribarren Josean A , Moreno Leopoldo Muñoz , Quero José Hernández , Villar-García Judit , Knobel Hernando , Barrufet Pilar , Force Lluís , Casadellà Maria , Paredes Roger , Noguera-Julian Marc 
Published: August 2020

Background

Transmission of resistance mutations to integrase strand transfer inhibitors (INSTIs) in HIV-infected patients may compromise the efficacy of first-line antiretroviral regimens currently recommended worldwide. Continued surveillance of transmitted drug resistance (TDR) is thus warranted.

Objectives

We evaluated the rates and effects on virological outcomes of TDR in a 96 week prospective multicentre cohort study of ART-naive HIV-1-infected subjects initiating INSTI-based ART in Spain between April 2015 and December 2016.

Methods

Pre-ART plasma samples were genotyped for integrase, protease and reverse transcriptase resistance using Sanger population sequencing or MiSeq™ using a ≥ 20% mutant sensitivity cut-off. Those present at 1%–19% of the virus population were considered to be low-frequency variants.

Results

From a total of 214 available samples, 173 (80.8%), 210 (98.1%) and 214 (100.0%) were successfully amplified for integrase, reverse transcriptase and protease genes, respectively. Using a Sanger-like cut-off, the overall prevalence of any TDR, INSTI-, NRTI-, NNRTI- and protease inhibitor (PI)-associated mutations was 13.1%, 1.7%, 3.8%, 7.1% and 0.9%, respectively. Only three (1.7%) subjects had INSTI TDR (R263K, E138K and G163R), while minority variants with integrase TDR were detected in 9.6% of subjects. There were no virological failures during 96 weeks of follow-up in subjects harbouring TDR as majority variants.

Conclusions

Transmitted INSTI resistance remains rare in Spain and, to date, is not associated with virological failure to first-line INSTI-based regimens.