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Basic Characteristics of Mutations
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Mutation Site
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K101E |
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Mutation Site Sentence
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Some RT variants became dominant at VF (K101E, 86.3%;Y181C, 100.0%;G190A, 100.0%) and others emerged in integrase (Y143C, 2.4%;Q148R, 6.2%;N155H, 18.8%). |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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RT |
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Standardized Encoding Gene
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gag-pol:155348
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Genotype/Subtype
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HIV-1 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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HIV Infections
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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Y |
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Treatment
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etravirine (ETR) |
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Location
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Caucasian;sub-Saharan Africa |
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Literature Information
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PMID
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32259255
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Title
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Characterization of viral rebounds on dual etravirine/raltegravir maintenance therapy (ANRS-163 ETRAL trial)
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Author
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Soulie C,Assoumou L,Abdi B,Sayon S,Nguyen T,Valantin MA,Beniguel L,Ferre V,Alloui C,Montes B,Avettand-Fenoel V,Delaugerre C,Descamps D,Martinez E,Reynes J,Peytavin G,Costagliola D,Katlama C,Calvez V,Marcelin AG
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Journal
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The Journal of antimicrobial chemotherapy
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Journal Info
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2020 Jul 1;75(7):1943-1949
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Abstract
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BACKGROUND: The ANRS-163 ETRAL trial, a switch study to an etravirine 200 mg/raltegravir 400 mg twice-daily regimen in 165 patients with HIV-1 infection, showed durable efficacy until Week 96. The aim of this work was to investigate in detail the virological rebounds (VRs), defined as at least one plasma HIV viral load (VL) >50 copies/mL. METHODS: Quantification of HIV-DNA level was assessed at baseline, Week 48 and Week 96 (n = 157). VLs were measured in seminal plasma at Week 48 (n = 26). Genotypic resistance testing by ultra-deep sequencing (UDS) for reverse transcriptase (RT) and integrase regions was performed at baseline and at the time of VR. RESULTS: In this study, 19 patients experienced VR, with 2 patients having virological failure (VF; two consecutive VLs >50 copies/mL). For the first patient with VF, UDS detected minority resistant variants only in RT (K103N, 9.6%; Y181C, 4.9%) at baseline. Some RT variants became dominant at VF (K101E, 86.3%; Y181C, 100.0%; G190A, 100.0%) and others emerged in integrase (Y143C, 2.4%; Q148R, 6.2%; N155H, 18.8%). For the second patient with VF, neither RT nor integrase mutations were detected at baseline and VF. Median HIV-DNA level was similar at baseline, Week 48 and Week 96 (2.17, 2.06 and 2.11 log10 copies/106 cells, respectively). Only one patient had a detectable seminal HIV VL (505 copies/mL). CONCLUSIONS: The dual etravirine/raltegravir regimen as maintenance therapy was effective and the emergence of mutations in cases of VF was similar to that seen in other dual-regimen studies. No HIV-DNA level modification was evidenced by Week 96.
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Sequence Data
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-
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