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Basic Characteristics of Mutations
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Mutation Site
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Q148H |
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Mutation Site Sentence
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The major INSTI-RMs that more frequently emerged were: N155H (17.8%), G140S (8.4%), Y143R (7.5%), Q148H (6.5%), and Y143C (4.7%). |
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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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IN |
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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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INSTIs |
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Location
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Italian |
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Literature Information
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PMID
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31330378
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Title
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Evaluation of HIV-1 integrase resistance emergence and evolution in patients treated with integrase inhibitors
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Author
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Scutari R,Alteri C,Vicenti I,Di Carlo D,Zuccaro V,Incardona F,Borghi V,Bezenchek A,Andreoni M,Antinori A,Perno CF,Cascio A,De Luca A,Zazzi M,Santoro MM
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Journal
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Journal of global antimicrobial resistance
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Journal Info
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2020 Mar;20:163-169
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Abstract
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OBJECTIVES: This study evaluated the emergence of mutations associated with integrase strand transfer inhibitors (INSTI) resistance (INSTI-RMs) and the integrase evolution in human immunodeficiency virus type 1 (HIV-1) infected patients treated with this drug class. METHODS: The emergence of INSTI-RMs and integrase evolution (estimated as genetic distance between integrase sequences under INSTI treatment and before INSTI treatment) were evaluated in 107 INSTI-naive patients (19 drug-naive and 88 drug-experienced) with two plasma genotypic resistance tests: one before INSTI treatment and one under INSTI treatment. A logistic regression analysis was performed to evaluate factors associated with the integrase evolution under INSTI treatment. RESULTS: The patients were mainly infected by B subtype (72.0%). Eighty-seven patients were treated with raltegravir, 13 with dolutegravir and seven with elvitegravir. Before INSTI treatment one patient harboured the major INSTI-RM R263K and three patients the accessory INSTI-RMs T97A. Under INSTI treatment the emergence of >/=1 INSTI-RM was found in 39 (36.4%) patients. The major INSTI-RMs that more frequently emerged were: N155H (17.8%), G140S (8.4%), Y143R (7.5%), Q148H (6.5%), and Y143C (4.7%). Concerning integrase evolution, a higher genetic distance was found in patients with >/=1 INSTI-RM compared with those without emergence of resistance (0.024 [0.012-0.036] vs. 0.015 [0.009-0.024], P=0.018). This higher integrase evolution was significantly associated with a longer duration of HIV-1 infection, a higher number of past regimens and non-B subtypes. CONCLUSIONS: These findings confirm that major INSTI-RMs very rarely occur in INSTI-naive patients. Under INSTI treatment, selection of drug-resistance follows the typical drug-resistance pathways; a higher evolution characterises integrase sequences developing drug-resistance compared with those without any resistance.
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Sequence Data
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-
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