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Spectrum of Atazanavir‐Selected Protease Inhibitor‐Resistance Mutations

2022-05Artigo científico Acesso aberto
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dc.contributor.authorthe EuResist Network Study Group
dc.contributor.authorAbecasis, Ana B.
dc.contributor.institutionTB, HIV and opportunistic diseases and pathogens (THOP)
dc.contributor.institutionGlobal Health and Tropical Medicine (GHTM)
dc.contributor.institutionInstituto de Higiene e Medicina Tropical (IHMT)
dc.contributor.pblMDPI - Multidisciplinary Digital Publishing Institute
dc.date.accessioned2022-06-21T22:25:15Z
dc.date.available2022-06-21T22:25:15Z
dc.date.issued2022-05
dc.descriptionFunding 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.
dc.description.abstractRitonavir‐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.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent740462
dc.identifier.doi10.3390/pathogens11050546
dc.identifier.issn2076-0817
dc.identifier.otherPURE: 44517717
dc.identifier.otherPURE UUID: a6987760-800c-410e-be4a-5cc86e037b4d
dc.identifier.otherScopus: 85130228606
dc.identifier.urihttp://hdl.handle.net/10362/140466
dc.identifier.urlhttps://www.scopus.com/pages/publications/85130228606
dc.language.isoeng
dc.peerreviewedyes
dc.subjectantiviral therapy
dc.subjectataza-navir
dc.subjectdrug resistance
dc.subjectHIV‐1
dc.subjectmutation
dc.subjectprotease
dc.subjectprotease inhibitor
dc.subjectImmunology and Allergy
dc.subjectMolecular Biology
dc.subjectGeneral Immunology and Microbiology
dc.subjectMicrobiology (medical)
dc.subjectInfectious Diseases
dc.subjectSDG 3 - Good Health and Well-being
dc.titleSpectrum of Atazanavir‐Selected Protease Inhibitor‐Resistance Mutationsen
dc.typejournal article
degois.publication.issue5
degois.publication.titlePathogens
degois.publication.volume11
dspace.entity.typePublication
rcaap.rightsopenAccess

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