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Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure

OBJECTIVES: We analysed the prevalence of M184V/I and/or K65R/E/N mutations archived in proviral DNA (pDNA) in youths with perinatal HIV, virological control and who previously carried these resistance mutations in historic plasma samples. METHODS: We included vertically HIV-infected youths/young ad...

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Autores principales: Jiménez de Ory, Santiago, Beltrán-Pavez, Carolina, Gutiérrez-López, Miguel, Santos, María Del Mar, Prieto, Luis, Sainz, Talía, Guillen, Sara, Aguilera-Alonso, David, Díez, Cristina, Bernardino, Jose Ignacio, Mellado, María José, Ramos, José Tomás, Holguín, África, Navarro, Marisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212770/
https://www.ncbi.nlm.nih.gov/pubmed/33734374
http://dx.doi.org/10.1093/jac/dkab080
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author Jiménez de Ory, Santiago
Beltrán-Pavez, Carolina
Gutiérrez-López, Miguel
Santos, María Del Mar
Prieto, Luis
Sainz, Talía
Guillen, Sara
Aguilera-Alonso, David
Díez, Cristina
Bernardino, Jose Ignacio
Mellado, María José
Ramos, José Tomás
Holguín, África
Navarro, Marisa
author_facet Jiménez de Ory, Santiago
Beltrán-Pavez, Carolina
Gutiérrez-López, Miguel
Santos, María Del Mar
Prieto, Luis
Sainz, Talía
Guillen, Sara
Aguilera-Alonso, David
Díez, Cristina
Bernardino, Jose Ignacio
Mellado, María José
Ramos, José Tomás
Holguín, África
Navarro, Marisa
author_sort Jiménez de Ory, Santiago
collection PubMed
description OBJECTIVES: We analysed the prevalence of M184V/I and/or K65R/E/N mutations archived in proviral DNA (pDNA) in youths with perinatal HIV, virological control and who previously carried these resistance mutations in historic plasma samples. METHODS: We included vertically HIV-infected youths/young adults aged ≥10 years in the Madrid Cohort of HIV-1 Infected Children and Adolescents, exposed to lamivudine and/or emtricitabine, with M184V/I and/or K65R/E/N in historic plasma samples, on antiretroviral therapy (ART), virologically suppressed (HIV-1 RNA <50 copies/mL), and with available PBMCs in the Spanish HIV BioBank. Genomic DNA was extracted from PBMCs and HIV-1 RT gene was amplified and sequenced for resistance testing by Stanford HIV Resistance tool. RESULTS: Among the 225 patients under follow-up in the study cohort, 13 (5.8%) met selection criteria, and RT sequences were recovered in 12 (92.3%) of them. All but one were Spaniards, carrying subtype B, with a median age at PBMCs sampling of 21.3 years (IQR: 15.6–23.1) with 4 years (IQR 2.1–6.5) of suppressed viral load (VL). Nine (75%) youths did not present M184V/I in pDNA after at least 1 year of viral suppression. In December 2019, the remaining three subjects carrying M184V/I in pDNA maintained suppressed viraemia, and two still used emtricitabine in ART. CONCLUSIONS: The prevalence of resistance mutations to lamivudine and emtricitabine in pDNA in a cohort of youths perinatally infected with HIV who remain with undetectable VL, previously lamivudine and/or emtricitabine experienced, was infrequent. Our results indicate that ART including lamivudine or emtricitabine may also be safe and successful in youths with perinatal HIV with previous experience of and resistances to these drugs detected in plasma.
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spelling pubmed-82127702021-06-21 Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure Jiménez de Ory, Santiago Beltrán-Pavez, Carolina Gutiérrez-López, Miguel Santos, María Del Mar Prieto, Luis Sainz, Talía Guillen, Sara Aguilera-Alonso, David Díez, Cristina Bernardino, Jose Ignacio Mellado, María José Ramos, José Tomás Holguín, África Navarro, Marisa J Antimicrob Chemother Original Research OBJECTIVES: We analysed the prevalence of M184V/I and/or K65R/E/N mutations archived in proviral DNA (pDNA) in youths with perinatal HIV, virological control and who previously carried these resistance mutations in historic plasma samples. METHODS: We included vertically HIV-infected youths/young adults aged ≥10 years in the Madrid Cohort of HIV-1 Infected Children and Adolescents, exposed to lamivudine and/or emtricitabine, with M184V/I and/or K65R/E/N in historic plasma samples, on antiretroviral therapy (ART), virologically suppressed (HIV-1 RNA <50 copies/mL), and with available PBMCs in the Spanish HIV BioBank. Genomic DNA was extracted from PBMCs and HIV-1 RT gene was amplified and sequenced for resistance testing by Stanford HIV Resistance tool. RESULTS: Among the 225 patients under follow-up in the study cohort, 13 (5.8%) met selection criteria, and RT sequences were recovered in 12 (92.3%) of them. All but one were Spaniards, carrying subtype B, with a median age at PBMCs sampling of 21.3 years (IQR: 15.6–23.1) with 4 years (IQR 2.1–6.5) of suppressed viral load (VL). Nine (75%) youths did not present M184V/I in pDNA after at least 1 year of viral suppression. In December 2019, the remaining three subjects carrying M184V/I in pDNA maintained suppressed viraemia, and two still used emtricitabine in ART. CONCLUSIONS: The prevalence of resistance mutations to lamivudine and emtricitabine in pDNA in a cohort of youths perinatally infected with HIV who remain with undetectable VL, previously lamivudine and/or emtricitabine experienced, was infrequent. Our results indicate that ART including lamivudine or emtricitabine may also be safe and successful in youths with perinatal HIV with previous experience of and resistances to these drugs detected in plasma. Oxford University Press 2021-03-18 /pmc/articles/PMC8212770/ /pubmed/33734374 http://dx.doi.org/10.1093/jac/dkab080 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Research
Jiménez de Ory, Santiago
Beltrán-Pavez, Carolina
Gutiérrez-López, Miguel
Santos, María Del Mar
Prieto, Luis
Sainz, Talía
Guillen, Sara
Aguilera-Alonso, David
Díez, Cristina
Bernardino, Jose Ignacio
Mellado, María José
Ramos, José Tomás
Holguín, África
Navarro, Marisa
Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure
title Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure
title_full Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure
title_fullStr Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure
title_full_unstemmed Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure
title_short Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure
title_sort prevalence of m184v and k65r in proviral dna from pbmcs in hiv-infected youths with lamivudine/emtricitabine exposure
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212770/
https://www.ncbi.nlm.nih.gov/pubmed/33734374
http://dx.doi.org/10.1093/jac/dkab080
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