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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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Among patients receiving D/C/F/TAF (n = 1949), none had post-baseline darunavir, primary PI, or tenofovir RAMs;only two (0.1%) patients developed an emtricitabine RAM, M184V/I. |
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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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- |
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Treatment
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NRTIs;emtricitabine |
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Location
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Argentina;Australia;Belgium;Brazil;Canada;France;Germany;Italy;Mexico;Puerto Rico (U.S. territory);South Africa;Spain;Thailand;United Kingdom;United States |
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Literature Information
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PMID
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32715952
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Title
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Pooled resistance analyses of darunavir once-daily regimens and formulations across 10 clinical studies of treatment-naive and treatment-experienced patients with human immunodeficiency virus-1 infection
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Author
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Lathouwers E,Seyedkazemi S,Luo D,Brown K,De Meyer S,Wong EY
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Journal
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HIV research & clinical practice
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Journal Info
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2020 Apr-Jun;21(2-3):83-89
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Abstract
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BACKGROUND: The efficacy and high barrier to resistance of darunavir have been demonstrated across diverse populations with HIV-1 infection. OBJECTIVE: To evaluate post-baseline resistance among patients in studies of once-daily (QD) darunavir-based regimens and formulations. METHODS: The analysis included treatment-naive and virologically failing or suppressed patients from 10 phase 2/3 studies (48-192 weeks in duration) of boosted darunavir 800 mg QD-based regimens. Three were phase 3 studies of the QD darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg single-tablet regimen. Post-baseline resistance was evaluated upon protocol-defined virologic failure (PDVF). Resistance-associated mutations (RAMs) were identified using International Antiviral Society-USA mutation lists. Phenotypic analyses varied across studies. RESULTS: Overall, 250 of 3635 patients in the analysis met PDVF criteria; 205 had post-baseline genotypes/phenotypes. In total, four (0.1%) patients developed (or had identified) >/=1 darunavir and/or primary protease inhibitor (PI) RAM; only one (<0.1%) patient (with prior lopinavir virologic failure) lost darunavir phenotypic susceptibility. Among 3317 patients using nucleos(t)ide reverse transcriptase inhibitors (N[t]RTIs; mostly emtricitabine and tenofovir), 13 (0.4%) had >/=1 N(t)RTI RAM (10 with M184I/V). Among patients receiving D/C/F/TAF (n = 1949), none had post-baseline darunavir, primary PI, or tenofovir RAMs; only two (0.1%) patients developed an emtricitabine RAM, M184V/I. CONCLUSIONS: Across a large, diverse population using darunavir 800 mg QD-based regimens and formulations, resistance development remains rare. After clinical trials that span >10 years, loss of phenotypic susceptibility to darunavir was only observed once in a PI-experienced patient and has never been observed in treatment-naive patients, treatment-experienced PI-naive patients, or treatment-experienced virologically suppressed patients.
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Sequence Data
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-
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