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Basic Characteristics of Mutations
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Mutation Site
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M184I |
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Mutation Site Sentence
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Preexisting archived M184V/I (all detected as mixtures with wild-type) was observed in 4/322 participants in the DTG/3TC group and 3/321 in the TAF-based regimen group. |
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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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DTG/3TC;TAF |
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Location
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African American;African heritage;Asian |
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Literature Information
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PMID
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31905383
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Title
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Efficacy and Safety of Switching to Dolutegravir/Lamivudine Fixed-Dose 2-Drug Regimen vs Continuing a Tenofovir Alafenamide-Based 3- or 4-Drug Regimen for Maintenance of Virologic Suppression in Adults Living With Human Immunodeficiency Virus Type 1: Phase 3, Randomized, Noninferiority TANGO Study
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Author
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van Wyk J,Ajana F,Bisshop F,De Wit S,Osiyemi O,Portilla Sogorb J,Routy JP,Wyen C,Ait-Khaled M,Nascimento MC,Pappa KA,Wang R,Wright J,Tenorio AR,Wynne B,Aboud M,Gartland MJ,Smith KY
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Journal
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Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
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Journal Info
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2020 Nov 5;71(8):1920-1929
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Abstract
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BACKGROUND: The 2-drug regimen dolutegravir (DTG) + lamivudine (3TC) is indicated for treatment-naive adults with human immunodeficiency virus type 1 (HIV-1). We present efficacy and safety of switching to DTG/3TC in virologically suppressed individuals. METHODS: TANGO is an open-label, multicenter, phase 3 study that randomized adults (1:1, stratified by baseline third agent class) with HIV-1 RNA <50 copies/mL to switch to once-daily fixed-dose DTG/3TC or remain on a tenofovir alafenamide (TAF)-based regimen. The primary end point was proportion of participants with HIV-1 RNA >/=50 copies/mL at week 48 (US Food and Drug Administration Snapshot algorithm) in the intention-to-treat-exposed population (4% noninferiority margin). RESULTS: 743 adults were enrolled; 741 received >/=1 dose of study drug (DTG/3TC, N = 369; TAF-based regimen, N = 372). At week 48, proportion of participants with HIV-1 RNA >/=50 copies/mL receiving DTG/3TC was 0.3% (1/369) vs 0.5% (2/372) with a TAF-based regimen (adjusted treatment difference [95% confidence interval], -0.3 [-1.2 to .7]), meeting noninferiority criteria. No participants receiving DTG/3TC and 1 receiving a TAF-based regimen met confirmed virologic withdrawal criteria, with no emergent resistance at failure. Drug-related grade >/=2 adverse events and withdrawals due to adverse events occurred in 17 (4.6%) and 13 (3.5%) participants with DTG/3TC and 3 (0.8%) and 2 (0.5%) with a TAF-based regimen, respectively. CONCLUSIONS: DTG/3TC was noninferior in maintaining virologic suppression vs a TAF-based regimen at week 48, with no virologic failure or emergent resistance reported with DTG/3TC, supporting it as a simplification strategy for virologically suppressed people with HIV-1. CLINICAL TRIALS REGISTRATION: NCT03446573.
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Sequence Data
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-
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