M Casadellà1, J R Santos2, M Noguera-Julian1, R Micán-Rivera3, P Domingo4, A Antela5, J Portilla6, J Sanz7, M Montero-Alonso8, J Navarro9, M Masiá10, N Valcarce-Pardeiro11, A Ocampo12, L Pérez-Martínez13, J Pasquau14, M J Vivancos15, A Imaz16, P Carmona-Oyaga17, L Muñoz-Medina18, J Villar-García19, P Barrufet20, R Paredes1,2. 1. IrsiCaixa AIDS Research Institute, Badalona, Catalonia, Spain. 2. Lluita contra la SIDA Foundation, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. 3. University Hospital La Paz, Madrid, Spain. 4. Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 5. Infectious Diseases Unit, Santiago de Compostela Clinical University Hospital, Santiago de Compostela, Spain. 6. Hospital General Universitario de Alicante, Alicante, Spain. 7. University Hospital de La Princesa, Madrid, Spain. 8. Infectious Diseases Unit, La Fe University and Polytechnic Hospital, Valencia, Spain. 9. Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain. 10. Infectious Diseases Unit, Elche University General Hospital, Elche, Spain. 11. Infectious Diseases Unit, Hospital Arquitecto Marcide, Ferrol, Spain. 12. HIV Unit, Hospital Álvaro Cunqueiro, Vigo, Spain. 13. Infectious Diseases Area, Hospital San Pedro-CIBIR, Logroño, Spain. 14. University Hospital Virgen de las Nieves, Granada, Spain. 15. Infectious Diseases Unit, Ramón y Cajal Hospital, Madrid, Spain. 16. HIV and STI Unit, Infectious Diseases Department, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain. 17. Infectious Diseases Unit, Donostia University Hospital, San Sebastián, Spain. 18. University Hospital San Cecilio, Granada, Spain. 19. Infectious Diseases Department, Hospital del Mar - IMIM, Barcelona, Spain. 20. Infectious Diseases Unit, Mataró Hospital, Mataró, Spain.
Abstract
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.
BACKGROUND: Transmission of resistance mutations to integrase strand transfer inhibitors (INSTIs) in HIV-infectedpatients 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.