Primary resistance to integrase strand transfer inhibitors in Spain using ultrasensitive HIV-1 genotyping.

Autor:	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
Předmět:	INTEGRASE inhibitors REVERSE transcriptase DRUG utilization PROTEASE inhibitors DRUG resistance COHORT analysis PNEUMOCYSTIS jiroveci PROTEINS HIV infections RESEARCH HIV integrase inhibitors GENETIC mutation RESEARCH methodology MEDICAL cooperation EVALUATION research COMPARATIVE studies ENZYMES GENOTYPES DRUG resistance in microorganisms HIV LONGITUDINAL method PHARMACODYNAMICS
Zdroj:	Journal of Antimicrobial Chemotherapy (JAC); Dec2020, Vol. 75 Issue 12, p3517-3524, 8p
Abstrakt:	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. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
Externí odkaz:	Zobrazit plný text záznamu