Spectrum of Atazanavir‐Selected Protease Inhibitor‐Resistance Mutations

Detalhes bibliográficos
Autor(a) principal: the EuResist Network Study Group
Data de Publicação: 2022
Outros Autores: Abecasis, Ana B.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/140466
Resumo: Funding Information: Conflicts of Interest: A.S. received research grants from Gilead Sciences, and personal fees for ad‐ visory boards from Gilead Sciences, MSD, and ViiV Healthcare, all outside the present work. M.Z. received research grants from Gilead Sciences, MSD, Theratechnologies and ViiV Healthcare and personal fees for advisory boards from Gilead Sciences, Janssen‐Cilag, MSD, Theratechnologies and ViiV Healthcare, all outside the present work. The funder had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Funding Information: Funding: S.‐Y.R., A.J.B. and R.W.S. were supported in part by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institute of Health (NIH) (award number AI136618). The work of O.T. and D.K. was supported by the Russian Science Foundation Grant No. 19‐75‐10097. A.B.A. received funding from Fundação para a Ciência e Tecnologia through projects PTDC/SAU‐ INF/31990/2017 (INTEGRIV) and PTDC/SAU‐PUB/4018/2021 (MARVEL). G.D.T. was supported by EuResist Network GEIE. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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spelling Spectrum of Atazanavir‐Selected Protease Inhibitor‐Resistance Mutationsantiviral therapyataza-navirdrug resistanceHIV‐1mutationproteaseprotease inhibitorImmunology and AllergyMolecular BiologyImmunology and Microbiology(all)Microbiology (medical)Infectious DiseasesSDG 3 - Good Health and Well-beingFunding Information: Conflicts of Interest: A.S. received research grants from Gilead Sciences, and personal fees for ad‐ visory boards from Gilead Sciences, MSD, and ViiV Healthcare, all outside the present work. M.Z. received research grants from Gilead Sciences, MSD, Theratechnologies and ViiV Healthcare and personal fees for advisory boards from Gilead Sciences, Janssen‐Cilag, MSD, Theratechnologies and ViiV Healthcare, all outside the present work. The funder had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Funding Information: Funding: S.‐Y.R., A.J.B. and R.W.S. were supported in part by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institute of Health (NIH) (award number AI136618). The work of O.T. and D.K. was supported by the Russian Science Foundation Grant No. 19‐75‐10097. A.B.A. received funding from Fundação para a Ciência e Tecnologia through projects PTDC/SAU‐ INF/31990/2017 (INTEGRIV) and PTDC/SAU‐PUB/4018/2021 (MARVEL). G.D.T. was supported by EuResist Network GEIE. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Ritonavir‐boosted atazanavir is an option for second‐line therapy in low‐ and middle-income countries (LMICs). We analyzed publicly available HIV‐1 protease sequences from previ-ously PI‐naïve patients with virological failure (VF) following treatment with atazanavir. Overall, 1497 patient sequences were identified, including 740 reported in 27 published studies and 757 from datasets assembled for this analysis. A total of 63% of patients received boosted atazanavir. A total of 38% had non‐subtype B viruses. A total of 264 (18%) sequences had a PI drug‐resistance mutation (DRM) defined as having a Stanford HIV Drug Resistance Database mutation penalty score. Among sequences with a DRM, nine major DRMs had a prevalence >5%: I50L (34%), M46I (33%), V82A (22%), L90M (19%), I54V (16%), N88S (10%), M46L (8%), V32I (6%), and I84V (6%). Common accessory DRMs were L33F (21%), Q58E (16%), K20T (14%), G73S (12%), L10F (10%), F53L (10%), K43T (9%), and L24I (6%). A novel nonpolymorphic mutation, L89T occurred in 8.4% of non‐subtype B, but in only 0.4% of subtype B sequences. The 264 sequences included 3 (1.1%) interpreted as causing high‐level, 14 (5.3%) as causing intermediate, and 27 (10.2%) as causing low‐level darunavir re-sistance. Atazanavir selects for nine major and eight accessory DRMs, and one novel nonpolymor-phic mutation occurring primarily in non‐B sequences. Atazanavir‐selected mutations confer low-levels of darunavir cross resistance. Clinical studies, however, are required to determine the optimal boosted PI to use for second‐line and potentially later line therapy in LMICs.TB, HIV and opportunistic diseases and pathogens (THOP)Global Health and Tropical Medicine (GHTM)Instituto de Higiene e Medicina Tropical (IHMT)RUNthe EuResist Network Study GroupAbecasis, Ana B.2022-06-21T22:25:15Z2022-052022-05-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/140466eng2076-0817PURE: 44517717https://doi.org/10.3390/pathogens11050546info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:17:34Zoai:run.unl.pt:10362/140466Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:49:40.047408Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Spectrum of Atazanavir‐Selected Protease Inhibitor‐Resistance Mutations
title Spectrum of Atazanavir‐Selected Protease Inhibitor‐Resistance Mutations
spellingShingle Spectrum of Atazanavir‐Selected Protease Inhibitor‐Resistance Mutations
the EuResist Network Study Group
antiviral therapy
ataza-navir
drug resistance
HIV‐1
mutation
protease
protease inhibitor
Immunology and Allergy
Molecular Biology
Immunology and Microbiology(all)
Microbiology (medical)
Infectious Diseases
SDG 3 - Good Health and Well-being
title_short Spectrum of Atazanavir‐Selected Protease Inhibitor‐Resistance Mutations
title_full Spectrum of Atazanavir‐Selected Protease Inhibitor‐Resistance Mutations
title_fullStr Spectrum of Atazanavir‐Selected Protease Inhibitor‐Resistance Mutations
title_full_unstemmed Spectrum of Atazanavir‐Selected Protease Inhibitor‐Resistance Mutations
title_sort Spectrum of Atazanavir‐Selected Protease Inhibitor‐Resistance Mutations
author the EuResist Network Study Group
author_facet the EuResist Network Study Group
Abecasis, Ana B.
author_role author
author2 Abecasis, Ana B.
author2_role author
dc.contributor.none.fl_str_mv TB, HIV and opportunistic diseases and pathogens (THOP)
Global Health and Tropical Medicine (GHTM)
Instituto de Higiene e Medicina Tropical (IHMT)
RUN
dc.contributor.author.fl_str_mv the EuResist Network Study Group
Abecasis, Ana B.
dc.subject.por.fl_str_mv antiviral therapy
ataza-navir
drug resistance
HIV‐1
mutation
protease
protease inhibitor
Immunology and Allergy
Molecular Biology
Immunology and Microbiology(all)
Microbiology (medical)
Infectious Diseases
SDG 3 - Good Health and Well-being
topic antiviral therapy
ataza-navir
drug resistance
HIV‐1
mutation
protease
protease inhibitor
Immunology and Allergy
Molecular Biology
Immunology and Microbiology(all)
Microbiology (medical)
Infectious Diseases
SDG 3 - Good Health and Well-being
description Funding Information: Conflicts of Interest: A.S. received research grants from Gilead Sciences, and personal fees for ad‐ visory boards from Gilead Sciences, MSD, and ViiV Healthcare, all outside the present work. M.Z. received research grants from Gilead Sciences, MSD, Theratechnologies and ViiV Healthcare and personal fees for advisory boards from Gilead Sciences, Janssen‐Cilag, MSD, Theratechnologies and ViiV Healthcare, all outside the present work. The funder had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Funding Information: Funding: S.‐Y.R., A.J.B. and R.W.S. were supported in part by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institute of Health (NIH) (award number AI136618). The work of O.T. and D.K. was supported by the Russian Science Foundation Grant No. 19‐75‐10097. A.B.A. received funding from Fundação para a Ciência e Tecnologia through projects PTDC/SAU‐ INF/31990/2017 (INTEGRIV) and PTDC/SAU‐PUB/4018/2021 (MARVEL). G.D.T. was supported by EuResist Network GEIE. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
publishDate 2022
dc.date.none.fl_str_mv 2022-06-21T22:25:15Z
2022-05
2022-05-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/140466
url http://hdl.handle.net/10362/140466
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2076-0817
PURE: 44517717
https://doi.org/10.3390/pathogens11050546
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eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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